Capsaicin-induced gastric mucosal hyperemia and protection: The role of calcitonin gene-related peptide

N. B. Merchant, D. T. Dempsey, M. W. Grabowski, M. Rizzo, W. P. Ritchie, B. Bass, D. Mercer, J. M. Kellum, S. Carvajal

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background. Topical capsaicin augments gastric mucosal blood flow and is cytoprotective. This phenomenon is blocked by nitric oxide (NO) synthase and cyclooxygenase inhibition. Capsaicin-sensitive neurons store and release calcitonin gene-related peptide (CGRP). The purpose of this investigation was to study the effects of a CGRP antagonist on capsaicin-induced hyperemia and protection and to determine the role of NO and the cytoprotective prostaglandin PGE2 in this process. Methods. The glandular stomachs in male Sprague-Dawley rats (280 to 350 gm) were chambered with the blood supply intact. Animals were divided into four groups. Normal saline solution (group 1) or the CGRP antagonists hCGRP8-37 (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). The gastric mucosa was then topically exposed to normal saline solution (pH 7.4), followed by 160 μmol/L capsaicin and then 10 mmol/L acidified taurocholate (pH 1.2), each for 15 minutes. Gastric mucosal blood flow (ml/min/100 gm tissue) was continuously measured (laser Doppler) and mucosal injury was assessed. Luminal PGE2 production was measured during the bile acid injury period by radioimmunoassay. Results. The CGRP antagonist hCGRP8-37 significantly inhibits capsaicin-induced hyperemia and its associated mucosal cytoprotection and also significantly decreases luminal mucosal PGE2 production. Pretreatment with L-arginine, but not D-arginine, reverses these effects of CGRP antagonism. Conclusions. CGRP is a mediator of capsaicin-induced hyperemia and protection. This effect may be dependent on both NO and PGE2 production.

Original languageEnglish (US)
Pages (from-to)419-425
Number of pages7
JournalSurgery
Volume116
Issue number2
StatePublished - Jan 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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    Merchant, N. B., Dempsey, D. T., Grabowski, M. W., Rizzo, M., Ritchie, W. P., Bass, B., Mercer, D., Kellum, J. M., & Carvajal, S. (1994). Capsaicin-induced gastric mucosal hyperemia and protection: The role of calcitonin gene-related peptide. Surgery, 116(2), 419-425.