A ROLE FOR CALCITONIN-GENE-RELATED PEPTIDE IN PROTECTION AGAINST GASTRIC-ULCERATION

Objective The goal of this investigation was to determine the role of calcitonin gene-related peptide (CGRP) in gastric mucosal resistance t o ulceration. Summary Background Data CGRP is a 37-amino acid peptide found in the peripheral ends of afferent gastric neurons. CGRP is know n to inhibit acid secretion, stimulate mucosal blood flow, and stimula te release of somatostatin. Methods The release of CGRP in response to intragastric and intra-arierial administration of capsaicin in the is olated, vascularly perfused rat stomach was measured by radioimmunoass ay. The molecular forms of CGRP released were analyzed by gel filtrati on chromatography. The effect of intravenous CGRP or intragastric caps aicin on gastric ulceration induced by 100 mmol/L HCI and indomethacin was studied in intact and endogenous CGRP-depieted rats. Results Intr a-arierial capsaicin (concentration range, 10(-7) to 10(-5) mol/L) sti mulated a prompt and sustained release of immunoreactive CGRP, of whic h 84% coeluted with rat 1-37 CGRP I by gel filtration. Intragastric ca psaicin (range, 10(-5) to 10(-4) mol/L) failed to release CGRP into th e vascular perfusate. In intact rats, intragastric capsaicin (10(-6) m ol/L) or intravenous CGRP I (10 mu g/kg/hr) reduced the number and are a of mucosal lesions caused by HCI and indomethacin compared with the findings in control rats. Rats depleted of endogenous CGRP were more s usceptible to gastric ulceration than were normal rats. Intragastric c apsaicin failed to protect the mucosa of CGRP-depleted rats, whereas e xogenous intravenous CGRP was effective. Conclusions These data suppor t the hypothesis that CGRP released from gastric enteric neurons media tes gastric mucosal resistance to ulceration by noxious agents.