Distribution of bradykinin B₂ receptors in sheep brain and spinal cord visualized by in vitro autoradiography

Bradykinin B₂ receptors were localized in the sheep brain and spinal cord by quantitative in vitro autoradiography using a radiolabelled and specific bradykinin B₂ receptor antagonist analogue, 3-4-hydroxyphenyl-propionyl-D-Arg⁰-[Hyp³,Thi⁵,D-Tic⁷,Oic⁸]bradykinin, (HPP-HOE140). This radioligand displays high affinity and specificity for bradykinin B₂ receptors. The respective K_i values of 0.32, 1.37 and 156 nM were obtained for bradykinin, HOE140 and D-Arg[Hyp³,D-Phe⁷,Leu⁸]bradykinin competing for radioligand binding to lamina II of sheep spinal cord sections. Using this radioligand, we have demonstrated the distribution of bradykinin B₂ receptors in many brain regions which have not been previously reported.

The highest density of bradykinin B₂ receptors occur in the pleoglial periaqueductal gray, oculomotor and trochlear nuclei and the circumventricular organs. Moderate densities of receptors occur in the substantia nigra, particularly the reticular part, the posterior thalamic and subthalamic nuclei, zona incerta, the red and pontine nuclei, some of the pretectal nuclei and in discrete layers of the superior colliculus. In the hindbrain, moderate levels of bradykinin B₂ receptor binding occur in the nucleus of the solitary tract, and in spinal trigeminal, inferior olivary, cuneate and vestibular nuclei. Laminae II, X and dorsal root ganglia display the most striking binding densities in the spinal cord, while the remainder of the dorsal and ventral horn display a low and diffuse density of binding. Bradykinin B₂ receptors are extensively distributed throughout the sheep brain and spinal cord, not only to sensory areas but also to areas involved in motor activity. J. Comp. neurol. 381:203-218, 1997. © 1997 Wiley-Liss, Inc.