Calcitonin and CGRP inhibit gastrointestinal transit via distinct neuronal pathways

Abstract

This study compares the central nervous system effects of rat calcitonin and rat calcitonin gene-related peptide (CGRP) on gastrointestinal transit in freely moving rats. Calcitonin and CGRP (0.01-1.0 nmol) injected into the lateral cerebral ventricle significantly inhibited gastric emptying and small bowel transit but did not affect large bowel transit. These biological actions were abolished by ganglionic blockade with chlorisondamine but not by noradrenergic blockade with bretylium. Truncal vagotomy abolished the inhibitory effects of CGRP but not those of calcitonin. Neither adrenalectomy nor hypophysectomy prevented the inhibitory actions of calcitonin and CGRP on gastric emptying and small bowel transit. Intraperitoneal administration of calcitonin and CGRP (1 nmol) produced inhibition of gastric emptying only, and this was not abolished by ganglionic blockade. These results indicate that calcitonin and CGRP exhibit similar central nervous system effects, producing inhibition of gastric emptying and small bowel transit but not altering large bowel transit. Calcitonin inhibits gastrointestinal transit via nonvagal, nonnoradrenergic autonomic efferents, yet CGRP inhibits gastrointestinal transit via vagal efferent fibers.