Capsaicin-induced gastric mucosal hyperemia and protection: the role of calcitonin gene-related peptide.
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 mumol/L capsaicin and then 100 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.
Merchant
N B
NB
Frederick A. Reichle Surgical Research Laboratory, Department of Surgery, Temple University Hospital, Philadelphia, PA 19140.
Dempsey
D T
DT
Grabowski
M W
MW
Rizzo
M
M
Ritchie
W P
WP
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D006940:Hyperemia / Q000139:chemically induced*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D019323:omega-N-Methylarginine
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004247:DNA; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D002211:Capsaicin