Calcitonin gene-related peptide mediates the gastric hyperemic response to acid back-diffusion.
Disruption of the gastric mucosal barrier with resultant increased acid back-diffusion leads to a marked increase in gastric mucosal blood flow (GMBF). This increase in GMBF is blocked by ablation of capsaicin-sensitive sensory neurons. The gastric arterioles are densely innervated by afferent neurons containing vasodilator peptides, calcitonin gene-related peptide (CGRP) being the most potent of these. We investigated (a) whether CGRP is the vasodilator mediator released by acid stimulation of capsaicin-sensitive sensory neurons and (b) whether the resultant hyperemia protects against the acid-induced mucosal injury. When the stomach was perfused with 0.15N HCl plus 15% ethanol, GMBF significantly increased by 70%. This hyperemic response was completely blocked by intra-arterial infusion of human CGRP8-37 (500 pmol/min), a CGRP-receptor antagonist, close to the stomach. With the blockade of the hyperemic response to acid back-diffusion, gross and histological mucosal damage were significantly aggravated. It is concluded that CGRP mediates the gastric hyperemic response to acid back-diffusion and that this gastric hyperemic response is an important protective factor against acid-induced injury.
Li
D S
DS
Department of Medicine, University of California, Los Angeles.
Raybould
H E
HE
Quintero
E
E
Guth
P H
PH
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology* / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D004058:Diffusion; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D006851:Hydrochloric Acid / Q000633:toxicity; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects
D010446:Peptide Fragments; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C058636:calcitonin gene-related peptide (8-37); D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide; D006851:Hydrochloric Acid; D002211:Capsaicin