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Calcitonin gene-related peptide (CGRP) is present in the stomach, and exogenous CGRP stimulates gastric somatostatin release. A study was undertaken to elucidate the functional linkage between CGRP and somatostatin in the stomach. Newborn Wistar rats were made CGRP deficient by intraperitoneal injection of capsaicin 2 days after birth, and then 2.5 mo later, release of CGRP and somatostatin was examined by vascular perfusion of the isolated stomach. In CGRP-deficient rats, neither the content nor basal secretion of gastric somatostatin differed from that in normal rats, and although none of several secretagogues induced CGRP secretion, the somatostatin response to glucagon was well preserved, indicating the presence of normally functioning D cells. On the other hand, arterial infusion of capsaicin significantly increased the release of not only CGRP but also somatostatin from the stomach of normal rats. In CGRP-deficient rats, however, capsaicin produced no corresponding effect. Finally, human CGRP-(8-37), a CGRP-receptor antagonist, completely inhibited the increase of gastric somatostatin induced by both rat alpha-CGRP and capsaicin infusion in normal rats. Thus the capsaicin-induced increase of somatostatin release appears to be mediated by CGRP in the stomach.
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