CAPSAICIN-INDUCED GASTRIC-MUCOSAL HYPEREMIA AND PROTECTION - THE ROLEOF CALCITONIN-GENE-RELATED PEPTIDE

Background. Topical capsaicin augments gastric mucosal blood flow and is cytoprotective. This phenomenon is blocked by nitric oxide (NO) syn thase and cyclooxygenase inhibition. Capsaicin-sensitive neurons store and release calcitonin gene-related peptide (CGRP). The purpose of th is investigation was to study the effects of a CGRP antagonist on caps aicin-induced hyperemia and protection and to determine the role of NO and the cytoprotective prostaglandin PGE(2) in this process. Methods. The glandular stomachs in male Sprague-Dawley rats (280 to 350 gm) we re chambered with the blood supply intact. Animals were divided into f our groups. Normal saline solution (group 1) or the CGRP antagonists h CGRP(8.37) (groups 2 through 4, 0.047 mg/ml) were continuously infused intraarterially via a retrograde splenic artery catheter at a rate of 0.034 ml/min after rats were given an intravenous bolus of either NSS (groups 1 and 2), L-arginine (group 3), or D-arginine (group 4) (200 mg/kg). These gastric mucosa was then topically exposed to normal sali ne solution (pH 7.4), followed by 160 mu mol/L capsaicin and then 10 m mol/L acidified taurocholate (pH 1.2), each for 15 minutes. Gastric mu cosal blood flow (ml/min/100 gm tissue) was continuously measured (las er Doppler) and mucosal injury was assessed. Luminal PGE(2) production was measured during the bile acid injury period by radioimunoassay. R esults. The CGRP antagonist hCGRP(8.37) significantly inhibits capsaic in-induced hyperemia and its associated mucosal cytoprotection and als o significantly decreases luminal mucosal PGE(2) production. Pretreatm ent with L-arginine, but not D-arginine, reverses these effects of CGR P antagonism. Conclusions. CGRP is a mediator of capsaicin-induced hyp eremia and protection. This effect may be dependent on both NO and PGE (2) production.