Lack of effect of the adenosine A1 receptor agonist, GR79236, on capsaicin-induced CGRP release in anaesthetized pigs
U Arulmani
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Search for more papers by this authorJPC Heiligers
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Search for more papers by this authorD Centurión
Departamento de Farmacobiología, CINVESTAV-IPN, Col. Granjas-Coapa, México
Search for more papers by this authorIM Garrelds
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Search for more papers by this authorCM Villalón
Departamento de Farmacobiología, CINVESTAV-IPN, Col. Granjas-Coapa, México
Search for more papers by this authorCorresponding Author
PR Saxena
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Prof. Dr Pramod R. Saxena, Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, the Netherlands, Tel. + 31 1 0408 7537/47, fax + 31 1 0408 9458, e-mail [email protected]Search for more papers by this authorU Arulmani
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Search for more papers by this authorJPC Heiligers
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Search for more papers by this authorD Centurión
Departamento de Farmacobiología, CINVESTAV-IPN, Col. Granjas-Coapa, México
Search for more papers by this authorIM Garrelds
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Search for more papers by this authorCM Villalón
Departamento de Farmacobiología, CINVESTAV-IPN, Col. Granjas-Coapa, México
Search for more papers by this authorCorresponding Author
PR Saxena
Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
Prof. Dr Pramod R. Saxena, Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Erasmus MC, University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, the Netherlands, Tel. + 31 1 0408 7537/47, fax + 31 1 0408 9458, e-mail [email protected]Search for more papers by this authorAbstract
Migraine is a common neurological disorder that is associated with an increase in plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a potent vasodilator released from the activated trigeminal sensory nerves, dilates intracranial blood vessels and transmits vascular nociception. Hence, inhibition of trigeminal CGRP release may prevent neurotransmission and, thereby, ameliorate migraine headache. Therefore, the present study in anaesthetized pigs investigates the effects of a selective adenosine A1 receptor agonist, GR79236 (3, 10 and 30 µg/kg, i.v.) on capsaicin-induced carotid haemodynamic changes and on plasma CGRP release. Intracarotid (i.c.) infusion of capsaicin (10 µg/kg/min, i.c.) increased the total carotid blood flow and conductance as well as carotid pulsations, but decreased the difference between arterial and jugular venous oxygen saturations. These responses to capsaicin were dose-dependently attenuated by GR79236. However, the increases in the plasma CGRP concentrations by capsaicin remained essentially unmodified after GR79236 treatment. The above results suggest that GR79236 may have an antimigraine potential due to its postjunctional effects (carotid vasoconstriction) rather than to prejunctional inhibition of trigeminal CGRP release.
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