Chapter 16
Smooth muscle of the gut
Gabriel M. Makhlouf,
Karnam S. Murthy,
Gabriel M. Makhlouf
Virginia Commonwealth University, Richmond, VA, USA
Search for more papers by this authorKarnam S. Murthy
Virginia Commonwealth University, Richmond, VA, USA
Search for more papers by this authorGabriel M. Makhlouf,
Karnam S. Murthy,
Gabriel M. Makhlouf
Virginia Commonwealth University, Richmond, VA, USA
Search for more papers by this authorKarnam S. Murthy
Virginia Commonwealth University, Richmond, VA, USA
Search for more papers by this authorBook Editor(s):Daniel K. Podolsky MD,
Michael Camilleri MD,
J. Gregory Fitz MD FAASLD,
Anthony N. Kalloo MD,
Fergus Shanahan MD,
Timothy C. Wang MD,
Daniel K. Podolsky MD
President, University of Texas Southwestern Medical Center, Professor of Internal Medicine, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX, USA
Search for more papers by this authorMichael Camilleri MD
Executive Dean for Development, Atherton and Winifred W. Bean Professor, Professor of Medicine, Physiology and Pharmacology, Distinguished Investigator, Mayo Clinic, Rochester, MN, USA
Search for more papers by this authorJ. Gregory Fitz MD FAASLD
Executive Vice President for Academic Aff airs and Provost, University of Texas Southwestern Medical Center, Dean, Professor of Internal Medicine, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX, USA
Search for more papers by this authorAnthony N. Kalloo MD
Professor of Medicine, Johns Hopkins University School of Medicine, Director, Division of Gastroenterology & Hepatology, Johns Hopkins Hospital, Baltimore, MD, USA
Search for more papers by this authorFergus Shanahan MD
Professor and Chair, Department of Medicine, Director, Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland
Search for more papers by this authorTimothy C. Wang MD
Chief, Division of Digestive and Liver Diseases, Silberberg Professor of Medicine, Department of Medicine and Irving Cancer Research Center, Columbia University Medical Center, New York, NY, USA
Search for more papers by this authorFirst published: 27 November 2015
Summary
The main function of the smooth muscle of the gut is to mix and propel intralumenal contents, enabling efficient digestion of food, progressive absorption of nutrients, and eventual evacuation of residues. This function is regulated by the intrinsic electrical and mechanical properties of smooth muscle, such as the ability to maintain tone or undergo phasic contraction, and by alterations in these properties in response to hormonal and neural signals, particularly signals emanating from the enteric nervous system. The signal transduction pathways present in isolated circular and longitudinal muscle cells regulate tonic contraction and relaxation of intact, syncytial muscle. Extrinsic neurons of the sympathetic and parasympathetic systems influence smooth muscle indirectly by acting on neurons of the myenteric plexus. The disparate changes in signaling triggered by inflammatory cytokines and induced by nuclear factor-kappa B in circular and longitudinal muscle disrupt the activity and functional coordination of the two muscle layers.
References
- Alemi F., Poole D.P., Chiu J., et al. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology 2013; 144: 145.
- Jin J.G., Murthy K.S., Grider J.R., et al. Stoichiometry of VIP release and NO formation during nerve stimulation of rabbit gastric muscle. Am J Physiol 1997; 271: G357.
- Klein S., Seider B., Kettenberger A., et al. Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity. Nat Commun 2013; 4: 1630.
- Murthy K.S. Signaling for contraction and relaxation in smooth muscle of the gut. Annu Rev Physiol 2006; 68: 345.
- Murthy K.S., Zhou H., Grider J.R., et al. Differential signaling by muscarinic receptors in smooth muscle: m2-mediated inactivation of MLC kinase via Gi3, Cdc42/Rac1 and p-21-activated kinase 1 pathway, and m3-mediated MLC20 phosphorylation via Rho-associated kinase/myosin phosphatase targeting subunit 1 and protein kinase C/CPI-17 pathway. Biochem J 2003; 374: 145.
- Narayanan D., Adebiyi A., Jaggar J.H. Inositol trisphosphate receptors in smooth muscle cells. Am J Physiol Heart Circ Physiol 2012; 302: H2190.
- Sanders K.M., Hwang S.J., Ward S.M. Neuroeffector apparatus in gastrointestinal smooth muscle organs. J Physiol 2010; 588: 4621.
- Shea-Donohue T., Notari L., Sun R., et al. Mechanisms of smooth muscle responses to inflammation. Neurogastroenterol Motil 2012; 24: 802.
- Szurszewski J.H. Electrical basis of gastrointestinal motility. In: L.R. Johnson (ed). Physiology of the Gastrointestinal Tract, 2nd ed. New York: Raven Press; 1987: 383.
- Gabella G. Structure of muscles and nerves in the gastrointestinal tract. In: LR Johnson (ed). Physiology of the Gastrointestinal Tract, 2nd ed. New York: Raven Press; 1987: 335.
- Gabella G. Structure of intestinal musculature. In: JD Wood (ed). Motility and Circulation. Handbook of Physiology, Vol. 1, Sect. 6: The Gastrointestinal System. New York: American Physiological Society; 1989: 103.
- Gabella G. Quantitative morphological study of smooth muscle cells of the guinea-pig teniae coli. Cell Tissue Res 1976; 170: 161.
- Okamoto T, Schlegel A, Scherer PE, et al. Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J Biol Chem 1998; 273: 5419.
- Shaul PE, Anderson RG. Role of plasmalemmal caveolae in signal transduction. Am J Physiol 1998; 275: L843.
- Murthy KS, Makhlouf GM. Heterologous desensitization mediated by G protein-specific binding to caveolin. J Biol Chem 2000; 275: 30211.
- Gerthoffer WT, Gunst SJ. Signal transduction in smooth muscle. Invited review: focal adhesion and small heat shock proteins in the regulation of actin remodeling and contractility in smooth muscle. J Appl Physiol 2001; 91: 963.
- Murphy RA. Contraction of muscle cells. In: RM Berne, MN Levy (eds). Physiology, 2nd ed. St Louis, MO: CV Mosby; 1988: 315.
- Gabella G, Blundell D. Gap junctions of the muscles of the small and large intestine. Cell Tissue Res 1981; 219: 469.
- Somlyo AP, Somlyo AV, Shuman H. Electron probe analysis of vascular smooth muscle. J Cell Biol 1979; 81: 316.
- Rayemakers L, Wuytack F, Batra S, et al. A comparative study of the calcium accumulation by mitochondria and microsomes isolated from the smooth muscle of the guinea-pig teniae coli. Pflugers Arch 1977; 368: 217.
- Bitar KN, Burgess GM, Putney JW Jr, et al. Source of activator calcium in isolated guinea pig and human gastric muscle cells. Am J Physiol 1986; 250: G280.
- Bitar KN, Bradford PJ, Putney JW Jr, et al. Stoichiometry of contraction and Ca2+ mobilization by inositol 1,4,5-triphosphate in isolated gastric smooth muscle cells. J Biol Chem 1986; 261: 16591.
- Berridge MJ, Irvine RF. Inositol phosphates and cell signaling. Nature 1989; 341: 197.
- Burgess GM, McKinney JS, Fabiato A, et al. Calcium pools in saponin-permeabilized guinea pig hepatocytes. J Biol Chem 1983; 258: 15336.
- Hartshorne DJ. Biochemistry of the contractile process in smooth muscle. In: LR Johnson (ed). Physiology of the Gastrointestinal Tract, 2nd ed. New York: Raven Press; 1987: 423.
- Bond M, Somlyo AV. Dense bodies and actin polarity in vertebrate smooth muscle. J Cell Biol 1982; 95: 403.
- Sobieszek A. Vertebrate smooth muscle myosin: enzymatic and structural properties. In: NL Stephen (ed). The Biochemistry of Smooth Muscle. Baltimore, MD: University Park Press; 1977: 413.
- Murphy RA. Muscle cells of hollow organs. News Physiol Sci 1988; 3: 124.
- Somlyo AP, Somlyo AP. Signal transduction and regulation in smooth muscle. Nature 1994; 372: 231.
- Somlyo AP, Somlyo AP. Ca2+ sensitivity of smooth muscle and non-muscle myosin II: modulated by G proteins, kinases and phosphatases. Physiol Rev 2003; 83: 1325.
- Murthy KS. Signaling for contraction and relaxation in smooth muscle of the gut. Annu Rev Physiol 2006; 68: 345.
- Kamm KE, Stull JT. Dedicated myosin light chain kinases with diverse cellular functions. J Biol Chem 2001; 276: 4527.
- Harshorne DJ, Eto M, Erodi F. Myosin light chain phosphatase: subunit composition, interaction and regulation. J Muscle Res Cell Motil 1998; 19: 325.
- Makhlouf GM, Murthy KS. Signal transduction in gastrointestinal smooth muscle. Cell Signal 1997; 9: 269.
- Sward K, Mita M, Wilson DP, et al. The role of RhoA and Rhoassociated kinase in vascular smooth muscle contraction. Curr Hypertens Rep 2003; 5: 66.
- Murthy KS, Zhou H, Grider JR, et al. Differential signaling by muscarinic receptors in smooth muscle: m2-mediated inactivation of MLC kinase via Gi3, Cdc42/Rac1 and p-21-activated kinase 1 pathway, and m3-mediated MLC20 phosphorylation via Rho-associated kinase/myosin phosphatase targeting subunit 1 and protein kinase C/CPI-17 pathway. Biochem J 2003; 374: 145.
- Lefkowitz RJ, Caron MG. Adrenergic receptors: models for the study of receptors coupled to guanine nucleotide regulatory proteins. J Biol Chem 1988; 263: 4993.
- Barnard EA. Separating receptor subtypes from their shadows. Nature 1988; 335: 381.
- Gilman AG. G proteins and regulation of adenylyl cyclases. Biosci Rep 1995; 15: 65.
- Hollinger S, Hepler JR. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Annu Rev Biochem 2002; 67: 653.
- Berridge MJ, Irvine RF. Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 1984; 312: 321.
- Exton JH. Regulation of phosphoinositide phospholipases by hormones, neurotransmitters, and other agonists linked to G proteins. Annu Rev Pharmacol Toxicol 1996; 36: 481.
- Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 1988; 334: 661.
- Murthy KS, Makhlouf GM. Phosphoinositide metabolism in intestinal smooth muscle: preferential production of Ins(1,4,5)P3 in circular muscle cells. Am J Physiol 1991; 261: G945.
- Cockcroft S, Thomas GMH. Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors. Biochem J 1992; 288: 1.
- Berridge MJ, Gallione A. Cytosolic calcium oscillators. FASEB J 1988; 2: 3074.
- McPherson PS, Campbell KP. The ryanodine receptor/Ca2+ release channel. J Biol Chem 1993; 268: 13765.
- Furuichi T, Yoshikawa S, Miyawaki A, et al. Primary structure and function expression of the inositol 1,4,5-triphosphate-binding protein P400. Nature 1989; 342: 32.
- Mignery GA, Sudhof TC, Takel K, et al. Putative receptor for inositol 1,4,5-triphosphate similar to ryanodine receptor. Nature 1989; 342: 192.
- Putney JW Jr, Broad LM, Braun FJ, et al. Mechanisms of capacitative calcium entry. J Cell Sci 2001; 114: 2223.
- Kitazawa T, Kobayashi S, Horiuti K, et al. Receptor-coupled permeabilized smooth muscle: role of the phosphatidyl-inositol cascade, G-proteins and modulation of the contractile response to Ca2. J Biol Chem 1989; 264: 5339.
- Kobayashi S, Somlyo AV, Somlyo AP. Heparin inhibits the inositol 1,4,5-triphosphate-dependent but not the independent calcium release induced by guanine nucleotide in vascular smooth muscle. Biochem Biophys Res Commun 1988; 153: 625.
- Bitar KN, Makhlouf GM. Receptors on smooth muscle cells: characterization by contraction and specific antagonists. Am J Physiol 1982; 242: G400.
- Bitar KN, Bradford P, Putney JW Jr, et al. Cytosolic calcium during contraction of isolated mammalian gastric muscle cells. Science 1986; 232: 1143.
- Grider JR, Makhlouf GM. Contraction mediated by Ca2+ release in circular and Ca2+ influx in longitudinal intestinal muscle cells. J Pharmacol Exp Ther 1988; 244: 432.
- Murthy KS, Makhlouf GM. Fluoride activates G protein-dependent and independent pathways in dispersed intestinal smooth muscle cells. Biochem Biophys Res Commun 1994; 202: 1681.
- Murthy KS, Grider JR, Makhlouf GM. InsP3-dependent Ca2+ mobilization in circular but not longitudinal muscle cells of intestine. Am J Physiol 1991; 261: G937.
- Makhlouf GM, Murthy KS. Cellular physiology of the gastrointestinal smooth muscle. In: LR Johnson (ed). Physiology of Gastrointestinal Tract, 4th ed. New York: Academic Press; 2006: 315.
- Kuemmerle JF, Murthy KS, Makhlouf GM. Agonist-activated, ryanodine-sensitive, IP3-insensitive Ca2+ release channels in longitudinal muscle of intestine. Am J Physiol 1994; 266: C1421.
- Murthy KS, Kuemmerle JF, Makhlouf GM. Agonist-mediated activation of PLA2 initiates Ca2+ in intestinal longitudinal smooth muscle. Am J Physiol 1995; 269: G93.
- Kuemmerle JF, Makhlouf GM. Activation of Cl− channels by contractile agonists depolarizes longitudinal muscle and triggers Ca2+ influx via voltage-sensitive Ca2+ channels. Gastroenterology 1994; 106: A527.
- Kuemmerle JF, Makhlouf GM. Agonist-stimulated cyclic ADP ribose: endogenous modulator of Ca2+-induced Ca2+-release in intestinal longitudinal muscle. J Biol Chem 1995; 270: 25488.
- Murthy KS, Zhou H, Grider JR, et al. Sequential activation of heterotrimeric and monomeric G proteins mediates PLD activity in smooth muscle. Am J Physiol Gastrointest Liver Physiol 2001; 280: G381.
- Murthy KS, Grider JR, Kuemmerle JF, et al. Sustained muscle contraction induced by agonists, growth factors, and Ca2+ mediated by distinct PKC isozymes. Am J Physiol Gastrointest Liver Physiol 2000; 279: G201.
- Harnett KM, Cao W, Biancani P. Signal transduction pathways that regulate smooth muscle function. I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal) sphincter smooth muscle. Am J Physiol Gastrointest Liver Physiol 2005; 288: G407.
- Murthy KS, Teng B-Q, Zhou H, et al. Gi1/Gi2-dependent signaling by single-transmembrane natriuretic peptide clearance receptor. Am J Physiol Gastrointest Liver Physiol 2000; 278: G974.
- Bitar KN, Makhlouf GM. Relaxation of isolated gastric smooth muscle cells by vasoactive intestinal peptide. Science 1982; 216: 531.
- Grider JR, Murthy KS, Jin JG, et al. Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol 1992; 262: G774.
- Murthy KS, Severi C, Grider JR, et al. Inhibition of inositol 1,4,5-triphosphate (IP3) production and IP3-dependent Ca2+ mobilization by cyclic nucleotides in isolated gastric muscle cells. Am J Physiol 1993; 264: G967.
- Murthy KS, Zhang K, Jin JG, et al. VIP-mediated G-protein-coupled Ca2+ influx activates a constitutive nitric oxide synthase in dispersed gastric muscle cells. Am J Physiol 1993; 265: G660.
- Murthy KS, Makhlouf GM. Interaction of cA-kinase and cG-kinase in mediating relaxation of dispersed smooth muscle cells. Am J Physiol 1995; 268: C171.
- Sunahara RK, Dessauer CW, Gilman AG. Complexity and diversity of mammalian adenylyl cyclases. Annu Rev Pharmacol Toxicol 1996; 36: 461.
- Murthy KS, Zhou H, Makhlouf GM. PKA-dependent activation of PDE3A and PDE4 and inhibition of adenylyl cyclase V/VI in smooth muscle. Am J Physiol Gastrointest Liver Physiol 2002; 282: C508.
- Francis SH, Turko IV, Corbin JD. Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Biol 2001; 65: 1.
- Murthy KS. Activation of phosphodiesterase 5 and inhibition of guanylate cyclase by cGMP-dependent protein kinase in smooth muscle. Biochem J 2001; 360: 199.
- Murthy KS. cAMP inhibits IP3-dependent Ca2+ release by preferential activation of cGMP-primed PKG. Am J Physiol Gastrointest Liver Physiol 2001; 281: G1238.
- Jin JG, Murthy KS, Grider JR, et al. Activation of cAMP- and cGMP-dependent pathways by relaxant agents in isolated gastric muscle cells. Am J Physiol 1993; 264: G470.
- Murthy KS, Zhou H, Grider JR, et al. Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially meditated by phosphorylation of RhoA. Am J Physiol Gastrointest Liver Physiol 2003; 284: G1006.
- Wooldridge AA, MacDonald JA, Erodi F, et al. Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of serine 695 in response to cyclic nucleotides. J Biol Chem 2004; 279: 34495.
- Walker LA, MacDonald JA, Liu X, et al. Site-specific phosphorylation and point mutations of telokin modulates its Ca2+-desensitizing effect in smooth muscle. J Biol Chem 2001; 276: 24519.
- Chasse SA, Dohlman HG. RGS proteins: G protein-coupled receptors meet their match. Assay Drug Dev Technol 2003; 1: 357.
- Casteels R. Membrane potential in smooth muscle cells. In: E Bulbring, AF Brading, AW Jones, et al. (eds). Smooth Muscle: An Assessment of Current Knowledge. Austin, TX: University of Texas Press; 1981: 105.
- Sanders KM. Electrophysiology of dissociated gastrointestinal muscle cells. In: JD Wood (ed). Motility and Circulation. Handbook of Physiology, Vol. 1, Sect. 6: The Gastrointestinal System. New York: American Physiological Society; 1989: 163.
- Szurszewski JH. Electrical basis of gastrointestinal motility. In: LR Johnson (ed). Physiology of the Gastrointestinal Tract, 2nd ed. New York: Raven Press; 1987: 383.
- Sanders KM, Smith TK. Electrophysiology of colonic smooth muscle. In: JD Wood (ed). Motility and Circulation. Handbook of Physiology, Vol. 1, Sect. 6: The Gastrointestinal System. New York: American Physiological Society; 1989: 251.
- Sanders KM, Publicover NG. Electrophysiology of gastric musculature. In: JD Wood (ed). Motility and Circulation. Handbook of Physiology, Vol. 1, Sect. 6: The Gastrointestinal System. New York: American Physiological Society; 1989: 187.
- Alberts B, Bray D, Lewis J, et al. Molecular Biology of the Cell. New York: Garland Publishing; 1983: 291.
- Walsh JV Jr, Singer JJ. Calcium action potentials in single freshly isolated smooth muscle cells. Am J Physiol 1980; 239: C162.
- Walsh JV Jr, Singer JJ. Voltage clamp of single freshly dissociated smooth muscle cells: current-voltage relationships for three currents. Pflugers Arch 1981; 390: 207.
- Singer JJ, Walsh JV Jr. Passive properties of the membrane of single freshly isolated smooth muscle cells. Am J Physiol 1980; 239: 153.
- Benham CD, Bolton TB. Patch-clamp studies of slow potentialsensitive potassium channels in longitudinal smooth muscle cells of rabbit jejunum. J Physiol 1983; 340: 469.
- Benham CD, Bolton TB, Lang RJ, et al. Calcium-activated potassium channels in single smooth muscle cells of rabbit jejunum and guinea-pig mesenteric artery. J Physiol 1986; 371: 45.
- Bolton TB, Lang RJ, Takewaki T, et al. Patch and whole-cell voltage clamp of single mammalian visceral and vascular smooth muscle cells. Experientia 1985; 41: 887.
- Andreas C, Sanders KM. Ca2+-activated K+ channels of canine colonic myocytes. Am J Physiol 1989; 257: C470.
- Ganitkevich VY, Shuba MF, Smirnov SV. Potential-dependent calcium inward current in a single isolated smooth muscle cell of the guinea-pig teniae caeci. J Physiol 1986; 380: 1.
- Droogmans G, Callewaert G. Ca2+-channel current and its modification by the dihydropyridine agonist BAY k8644 in isolated smooth muscle cells. Pflugers Arch 1986; 406: 259.
- Mitra R, Morad M. Ca2+ and Ca2+-activated K+ currents in mammalian gastric smooth muscle cells. Science 1985; 229: 269.
- Bechem M, Hebisch S, Schramm M. Ca2+ agonists: new, sensitive probes for Ca2+ channels. Trends Pharmacol Sci 1988; 9: 257.
- Singer JJ, Walsh JV Jr. Large conductance Ca2+ activated K+ channels in smooth muscle cell membrane. Biophys J 1984; 45: 68.
- Singer JJ, Walsh JV Jr. Characterization of calcium-activated potassium channels in single smooth muscle cells using the patch-clamp technique. Pflugers Arch 1987; 408: 98.
- Jin JG, Katsoulis S, Schmidt WE, et al. Inhibitory transmission in teniae coli mediated by distinct vasoactive intestinal peptide and apamin-sensitive pituitary adenylate cyclase activating peptide receptors. J Pharmacol Exp Ther 1994; 270: 433.
- Brown DA, Adams PR. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature 1980; 283: 673.
- Sims SM, Singer JJ, Walsh JV Jr. Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad. J Physiol 1985; 367: 503.
- Sims SM, Walsh JV Jr, Singer JJ. Substance P and acetylcholine both suppress the same K+ current in dissociated smooth muscle cells. Am J Physiol 1986; 251: C580.
- Thuneberg L. Interstitial cells of Cajal. In: JD Wood (ed). Motility and Circulation. Handbook of Physiology, Vol. 1, Sect. 6: The Gastrointestinal System. New York: American Physiological Society; 1989: 349.
- Burns AJ, Lomaz AEZ, Torihashi S, et al. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci U S A 1996; 93: 12008.
- Yamamoto M. Electron microscopic studies on the innervation of the smooth muscle and the interstitial cells of Cajal in the small intestine of the mouse and bat. Arch Histol Jpn 1977; 40: 171.
-
Ward SM,
Sanders KM.
Interstitial cells of Cajal: primary targets of enteric motor innervation.
Anat Rec
2001;
262:
125.
10.1002/1097-0185(20010101)262:1<125::AID-AR1017>3.0.CO;2-I CAS PubMed Web of Science® Google Scholar
- Ward SM. Interstitial cells of Cajal in enteric neurotransmission. Gut 2000; 47(Suppl 4): iv40.
- Sanders KM, Koh SD, Ward SM. Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu Rev Physiol 2006; 68: 307.
- Langton P, Ward SM, Carl A, et al. Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon. Proc Natl Acad Sci U S A 1989; 86: 7280.
- Ward SM, Burns AJ, Torihashi S, et al. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol 1994; 480: 91.
- Huizinga JD, Thuneberg L, Kluppel M, et al. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 1995; 373: 347.
- El-Sharkawy TY, Morgan KG, Szurszewski JH. Intracellular activity of canine and human gastric smooth muscle. J Physiol 1978; 279: 291.
- Szurszewski JH. Mechanism of action of pentagastrin and acetylcholine on the longitudinal muscle of the canine antrum. J Physiol 1975; 252: 335.
- Sanders KM. Colonic electrical activity: concerto for two pacemakers. News Physiol Sci 1989; 4: 176.
- Kobayashi S, Furness JB, Smith TK, et al. Histological identification of the interstitial cells of Cajal in the guinea-pig small intestine. Arch Histol Cytol 1989; 52: 267.
- Sanders KM, Ordog T, Koh SD, et al. A novel pacemaker mechanism drives gastrointestinal rhythmicity. News Physiol Sci 2000; 15: 291.
- Sanders KM, Burke EP, Stevens RJ. Effects of methylene blue on rhythmic activity and membrane potential in the canine proximal colon. Am J Physiol 1989; 256: G779.
- Hara Y, Kubota M, Szurszewski JH. Electrophysiology of the smooth muscle in the small intestine of some mammals. J Physiol 1986; 372: 501.
- Suzuki N, Prosser CL, Dahms V. Boundary cells between longitudinal and circular layers: essential for electrical slow waves in cat intestine. Am J Physiol 1986; 250: G287.
- Smith TK, Reed BJ, Sanders KM. Electrical pacemakers of canine proximal colon are functionally innervated by inhibitory motor neurons. Am J Physiol 1989; 256: C466.
- Smith TK. Spontaneous junction potentials and slow waves in the circular muscle of isolated segments of guinea-pig ileum. J Auton Nerv Syst 1989; 27: 147.
- Morgan KG, Szurszewski JH. Mechanisms of phasic and tonic actions of pentagastrin on canine gastric smooth muscle. J Physiol 1980; 301: 229.
- Morgan KG, Schmalz PF, Go VL, et al. Electrical and mechanical effects of molecular variants of CCK on antral smooth muscle. Am J Physiol 1978; 235: E324.
- Sanders KM, Vogalis F. Organization of electrical activity in the canine pyloric canal. J Physiol 1989; 416: 49.
- Morgan KG, Muir TC, Szurszewski JH. The electrical basis for contraction and relaxation in canine fundal smooth muscle. J Physiol 1981; 311: 475.
- Bauer AJ, Sanders KM. Gradient in excitation-contraction coupling in canine gastric antral circular muscle. J Physiol 1985; 369: 283.
- Smith TK, Reed BJ, Sanders KM. Interaction of two electrical pacemakers in muscularis of canine proximal colon. Am J Physiol 1987; 252: C290.
- Costa M, Brookes SJH, Steele PA, et al. Neurochemical classification of myenteric neurons in the guinea pig ileum. Neuroscience 1996; 75: 949.
- Costa M, Furness JB, Llewellyn-Smith IJ. Histochemistry of enteric nervous system. In: LR Johnson (ed). Physiology of the Gastrointestinal Tract, 2nd ed. New York: Raven Press; 1987: 1.
- Llewellyn IJ, Furness JB, Gibbins IL, et al. Quantitative ultrastructural analysis of enkephalin-, substance P-, and VIP-immunoreactive nerve fibers in the circular muscle of the guinea pig small intestine. J Comp Neurol 1988; 272: 139.
- Wilson AJ, Llewellyn-Smith IJ, Furness JB, et al. The source of the nerve fibres forming the deep muscular and circular muscle plexuses in the small intestine of the guinea-pig. Cell Tissue Res 1987; 247: 497.
- Watchow DA, Furness JB, Costa M. Distribution and coexistence of peptides in nerve fibers of the external muscle of the human gastrointestinal tract. Gastroenterology 1988; 95: 32.
- Costa M, Furness JB, Pompolo S, et al. Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea pig small intestine. Neurosci Lett 1992; 148: 121.
- Furness JB, Costa M. Identification of gastrointestinal neurotransmitters. In: G Bertaccini (ed). Handbook of Experimental Pharmacology: Mediators and Drugs in Gastrointestinal Motility, Vol. 59. Berlin: Springer-Verlag; 1982: 279.
- Makhlouf GM, Grider JR. Receptors for gut peptides on smooth muscle cells of the gut. In: GM Makhlouf (ed). Neural and Endocrine Biology of the Gut. Handbook of Physiology, Vol. 2, Sect. 6: The Gastrointestinal System. New York: American Physiological Society; 1989: 281.
- Makhlouf GM, Grider JR, Schubert ML. Identification of physiological function of gut peptides. In: GM Makhlouf (ed). Neural and Endocrine Biology of the Gut. Handbook of Physiology, Vol. 2, Sect. 6: The Gastrointestinal System. New York: American Physiological Society; 1989: 123.
- Makhlouf GM. Enteric neuropeptides: role in neuromuscular activity of the gut. Trends Pharmacol Sci 1985; 6: 214.
- Micheletti R, Grider JR, Makhlouf GM. Identification of bombesin receptors on isolated muscle cells from human intestine. Regul Pept 1988; 21: 219.
- Zetler G. Antagonism of the gut-contracting effects of bombesin and neurotensin by opioid peptides, morphine, atropine or tetrodotoxin. Pharmacology 1980; 21: 348.
- Yau WM, Lingle PF, Youther ML. Interaction of enkephalin and caerulein on guinea pig small intestine. Eur J Pharmacol 1983; 90: 245.
- Grider JR, Makhlouf GM. Regional and cellular heterogeneity of cholecystokinin receptors mediating muscle contraction in the gut. Gastroenterology 1987; 92: 175.
- Grider JR, Cable MB, Said SI, et al. Vasoactive intestinal peptide: relaxant neurotransmitter in teniae coli of the guinea pig. Gastroenterology 1985; 89: 36.
- Grider JR, Makhlouf GM. Suppression of inhibitory neural input to colonic circular muscle by opioid peptides. J Pharmacol Exp Ther 1987; 243: 205.
- Grider JR, Jin JG. VIP release and l-citrulline production from isolated ganglia of the myenteric plexus: evidence for regulation of VIP release by nitric oxide. Neuroscience 1993; 54: 521.
- Jin JG, Murthy KS, Grider JR, et al. Stoichiometry of VIP release and NO formation during nerve stimulation of rabbit gastric muscle. Am J Physiol 1997; 271: G357.
- Jin JG, Misra S, Grider JR, et al. Functional difference between substance P and neurokinin A: relaxation of gastric muscle by substance P is mediated by VIP and nitric oxide. Am J Physiol 1993; 264: G678.
- Grider JR, Katsoulis S, Schmidt WE, et al. Regulation of the descending relaxation phase of intestinal peristalsis by PACAP. J Auton Nerv Syst 1994; 50: 151.
- Grider JR. Interplay of VIP and nitric oxide in the regulation of the descending relaxation phase of peristalsis. Am J Physiol 1993; 264: G334.
- Murthy KS, Teng B-Q, Jin J-G, et al. G protein-dependent activation of smooth muscle eNOS via natriuretic peptide clearance receptor. Am J Physiol 1998; 275: C1409.
- Murthy KS, Makhlouf GM. VIP/PACAP-dependent activation of membrane-bound NO synthase in smooth muscle mediated by pertussis toxin-sensitive Gi1-2. J Biol Chem 1994; 269: 15977.
- Teng B, Murthy KS, Kuemmerle JF, et al. Expression of endothelial nitric oxide synthase in human and rabbit gastrointestinal smooth muscle cells. Am J Physiol 1998; 275: G342.
- Allescher HD, Kurjak M, Huber A, et al. Regulation of VIP release from rat enteric nerve terminals: evidence for a stimulatory effect of NO. Am J Physiol 1996; 271: G568.
- Murthy KS, Makhlouf GM. Identification of the G protein-activating domain of the natriuretic peptide clearance receptor (NPR-C). J Biol Chem 1999; 274: 17587.
- Murthy KS, Teng B-Q, Zhou H, et al. Gi1/Gi2-dependent signaling by single-transmembrane natriuretic peptide clearance receptor. Am J Physiol Gastrointest Liver Physiol 2000; 278: G974.
- Zhou H, Murthy KS. Identification of G-protein-activating sequence of the single-transmembrane natriuretic peptide receptor C (NPR-C). Am J Physiol 2003; 284: C1255.
- Murthy KS, Jin JG, Makhlouf GM. Inhibition of nitric oxide synthase activity in dispersed gastric muscle cells by protein kinase C. Am J Physiol 1994; 266: G161.
- Bitar KN, Makhlouf GM. Specific opiate receptors on isolated mammalian gastric smooth muscle cells. Nature 1982; 297: 72.
- Souquet JC, Grider JR, Bitar KN, et al. Receptors for mammalian tachykinins on isolated intestinal smooth muscle cells. Am J Physiol 1985; 249: G533.
- Biancani P, Walsh JH, Behar J. Vasoactive intestinal peptide: a neurotransmitter for relaxation of the rabbit internal anal sphincter. Gastroenterology 1985; 89: 867.
- Wiley JW, O'Dorisio TM, Owyang C. Vasoactive intestinal peptide mediated CCK-induced relaxation of sphincter of Oddi. J Clin Invest 1988; 81: 1920.
- Grider JR, Makhlouf GM. Colonic peristaltic reflex: identification of VIP as mediator of descending relaxation. Am J Physiol 1986; 251: G40.
- Grider JR. Identification of neurotransmitters regulating intestinal peristaltic reflex in humans. Gastroenterology 1989; 97: 1414.
- Grider JR. Tachykinins as transmitters of ascending contractile component of the peristaltic reflex. Am J Physiol 1989; 257: G709.
- Grider JR, Arimura A, Makhlouf GM. Role of somatostatin neurons in intestinal peristalsis: facilitatory interneurons in descending pathways. Am J Physiol 1987; 253: G434.
- Grider JR, Makhlouf GM. Role of opioid neurons in the regulation of intestinal peristalsis. Am J Physiol 1987; 253: G226.
- Grider JR. Interplay of somatostatin, opioid, and GABA neurons in the regulation of peristalsis reflex. Am J Physiol 1994; 267: G696.
- Grider JR, Makhlouf GM. Enteric GABA: mode of action and role in the regulation of the peristaltic reflex. Am J Physiol 1992; 262: G690.
- Grider JR. Regulation of excitatory neural input to longitudinal intestinal muscle by myenteric interneurons. Am J Physiol 1998; 275: G73.
- Grider JR, Jin JG. Distinct populations of sensory neurons mediate the peristaltic reflex elicited by muscle stretch and mucosal stimulation. J Neurosci 1994; 14: 2854.
- Grider JR. CGRP as a transmitter in the sensory pathway mediating peristaltic reflex. Am J Physiol 1994; 266: G1139.
- Grider JR, Kuemmerle JF, Jin JG. 5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4–5-HT1p receptors on sensory CGRP neurons. Am J Physiol 1996; 270: G778.
- Foxx-Orenstein AE, Kuemmerle JF, Grider JR. Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine. Gastroenterology 1996; 111: 1281.
- Grider JR, Foxx-Orenstein AE, Jin J-G. 5-hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine. Gastroenterology 1998; 115: 370.
- Foxx-Orenstein AE, Jin J-G, Grider JR. 5-HT4 receptor agonists and δ-opioid receptor antagonists act synergistically to stimulate colonic propulsion. Am J Physiol 1998; 275: G979.
- Jin J-G, Foxx-Orenstein AE, Grider JR. Propulsion in guinea pig colon induced by 5-hydroxytryptamine via 5-HT4 and 5-HT3 receptors. J Pharmacol Exp Ther 1999; 288: 93.
- Foxx-Orenstein AE, Grider JR. Regulation of colonic propulsion by enteric excitatory and inhibitory neurotransmitter. Am J Physiol 1996; 271: G433.
- Hall KE, Greenberg GR, El-Sharkawy TY, et al. Relationship between porcine motilin induced migrating motor complex-like activity, vagal integrity and endogenous motilin release in dogs. Gastroenterology 1984; 87: 76.
- Poitras P. Motilin is a digestive hormone in the dog. Gastroenterology 1984; 87: 909.
- Murthy KS, Makhlouf GM. Coexpression of ligand-gated P2X and G protein-coupled P2Y receptors in smooth muscle: preferential activation of P2Y receptors coupled to phospholipase C (PLC)-β1 via Gαq/11 and to PLC-β3 via Gβγi3. J Biol Chem 1998; 273: 4695.
- Murthy KS, Makhlouf GM. Adenosine A1 receptor-mediated activation of phospholipase C-β3 in intestinal muscle: dual requirement for α and βγ subunits of Gi3. Mol Pharmacol 1995; 47: 1172.
- Kuemmerle JF, Martin DC, Murthy KS, et al. Coexistence of contractile and relaxant 5-HT receptors coupled to distinct signaling pathways in intestinal muscle cells: convergence of the pathways on Ca2+ mobilization. Mol Pharmacol 1992; 42: 1090.
- Morini G, Kuemmerle JF, Impicciatore M, et al. Coexistence of histamine H1 and H2 receptors coupled to distinct signal transduction pathways in isolated intestinal muscle cells. J Pharmacol Exp Ther 1993; 264: 598.
- Rajagopal S, Kumar DP, Mahavadi S, et al. Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both EPac- and PKA-mediated inhibition of RhoA/Rho kinase pathway. Am J Physiol Gastrointest Liver Physiol 2013; 304: G527.
- Singer CA, Salinthone S, Baker KJ, et al. Synthesis of immune modulators by smooth muscle. Bioessays 2004; 26: 646.
- Shi X-Z, Sarna SK. Transcriptional regulation of inflammatory mediators secreted by human colonic circular smooth muscle cells. Am J Physiol Gastrointest Liver Physiol 2005; 289: G274.
- Cao W, Cheng L, Behar J, et al. Proinflammatory cytokines alter/reduce esophageal circular muscle contraction in experimental cat esophagitis. Am J Physiol 2004; 287: G1131.
- Akiho H, Blennerhassett P, Deng Y, et al. Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells. Am J Physiol Gastrointest Liver Physiol 2002; 282: G226.
- Shea-Donohue T, Urban JF Jr. Gastrointestinal parasite and host interactions. Curr Opin Gastroenterol 2004; 20: 3.
- Shi X-Z, Lindholm PF, Sarna SK. NF-kappa B activation by oxidative stress and inflammation suppresses contractility in colonic circular smooth muscle cells. Gastroenterology 2003; 124: 1369.
- Hu W, Mahavadi S, Li F, et al. Up-regulation of RGS4 and down-regulation of CP-17 mediate inhibition of colonic muscle contraction by interleukin-1β. Am J Physiol 2007; 293: C1991.
- Shi X-Z, Pazdrak K, Saada N, et al. Negative transcriptional regulation of human colonic smooth muscle Cav 1.2 channels by p50 and p65 subunits of NF-kappa B. Gastroenterology 2005; 129: 1518.
- Hu W, Li F, Mahavadi S, et al. Interleukin-1β up-regulates RGS4 through the canonical IKK2/IκBα/NF-κB pathway in rabbit colonic smooth muscle. Biochem J 2008; 412: 35.
- Hu W, Li F, Mahavadi S, et al. Upragulation of RGS4 expression IL-1β in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by PI3K/Akt/GSK3β pathway. Am J Physiol Cell Physiol 2009; 296: C1310.
- Cao W, Harnett KM, Cheng L, et al. H2O2: a mediator of esophagitisinduced damage to calcium-release mechanisms in cat lower esophageal sphincter. Am J Physiol Gastrointest Liver Physiol 2005; 288: G1170.
- Cao W, Vrees MD, Potenti FM, et al. Interleukin 1beta-induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis. J Pharmacol Exp Ther 2004; 311: 60.
- Hu W, Li F, Murthy KS. Interleukin-1β stimulates expression of NADPH oxidases NOX1 and NOX4 in colonic smooth muscle: mediation by NF-κB and differential modulation by c-jun kinase and ERK1/2. Gastroenterology 2006; 130: A505.
- Mahavadi S, Anderson CD, AlShboul O, et al. Identification of the signaling mechanisms that mediate hypercontractility during inflammation: activation of MLCK via NF-κB/PKA/AMPK pathway. Neurogastroenterol Motil 2010; 22: A307.
- Smith TK, Reed BJ, Sanders KM. Origin and propagation of electrical slow waves in circular muscle of canine proximal colon. Am J Physiol 1987; 252: C215.
