Neuroanatomical Localization, Pharmacological Characterization and Functions of CGRP, Related Peptides and Their Receptors

Potentiation of tachykinin-induced plasma protein extravasation by calcitonin gene-related peptide.

Characterization of the peptidergic afferent innervation of the stomach in the rat, mouse and guinea-pig

The origins of nerves containing calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and substance P were investigated in the rat stomach, pancreas, and colon, using immunocytochemistry combined with retrograde tracing and surgical and chemical denervation procedures. Compared with nerves containing vasoactive intestinal polypeptide (VIP) and galanin, which have primarily local origins in mammalian gut, CGRP-, NPY-, and substance P-immunoreactive nerves revealed dual extrinsic and intrinsic origins. Immunocytochemistry combined with retrograde tracing showed that the extrinsic CGRP- and substance P-immunoreactive nerves in the stomach and pancreas originate from bilateral dorsal root ganglia mainly at levels T8-T11, while those of the colon are derived from bilateral ganglia at S1 and, to a lesser extent, L1 and L6. Chemical denervations showed that neurons in these ganglia form a sensory input to the gut, and that those containing CGRP form the largest proportion. The results of combined retrograde tracing and immunocytochemistry indicated that extrinsic NPY-immunoreactive nerves originate from postganglionic sympathetic neurons lying in the coeliac and inferior mesenteric ganglia. These nerves were located mainly around blood vessels in gut and pancreas, showed sensitivity to 6-hydroxydopamine, and thus are likely to be noradrenergic. The present study provides a detailed mapping of the origins of some of the major peptide-containing nerves of the rat gastroenteropancreatic tract, thus providing further information on the anatomy of the enteric innervation.

https://www.jneurosci.org/content/jneuro/7/9/2674.full.pdf

Dual intrinsic and extrinsic origins of CGRP- and NPY-immunoreactive nerves of rat gut and pancreas

Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide generated from the alternate tissue-specific processing of the calcitonin gene mRNA.'.? Various forms (a and p ) of CGRP have been characterized from human tissue^.^-^ In the periphery, CGRP is co-localized and co-released with calcitonin in the parafollicular C cell of the thyroid gland,' with substance P in sensory nerves' and with acetylcholine in motoneurons.* In the brain, CGRP-like immunoreactivity is broadly distributed and especially concentrated in hypothalamic areas and some brainstem nuclei.9 A variety of biological effects have been claimed for CGRP, including the modulation of nicotinic receptor activities at the neuromuscularjunction'o*ll and of substance P in inflammation,\" a reduction of gastric acid s e c r e t i ~ n , ' ~ . ' ~ peripheral blood vessel dilation,Is cardiac a~celeration, '\" '~ a regulation of calcium metabolismh and insulin secretion\", an increase in body temperature, and a decrease in food intake. Iy-?' In spite of the various biological actions induced by CGRP, relatively little is known concerning the characteristics of its receptor~. '~,? '-?~ Consequently, a few years ago, our group undertook the development of selective agonists and antagonists which prove to be most useful for the identification of the existence of CGRP receptor s ~ b t y p e s . ' ~ ~ ~ ~ \" ' T h e various criteriaused to classify these receptor classes are reviewed here.

J.J. Hughes

Papers

Intraventricular calcitonin gene-related peptide inhibits gastric acid secretion