Calcitonin-gene related peptide can augment or prevent endothelin-1 induced gastric microvascular leakage.
The effects of locally infused calcitonin gene-related peptide (CGRP) on the changes in microvascular permeability and tissue injury following close-arterial infusion of endothelin-1 (5 pmol kg-1 min-1, 10 min) in the rat gastric mucosa have been investigated. Pretreatment with rat alpha-CGRP (10-50 pmol kg-1 min-1) inhibited the leakage of radiolabelled albumin and reduced the haemorrhagic necrosis, an action inhibited by the CGRP receptor antagonist, hCGRP-(8-37) (2 nmol kg-1 min-1). By contrast, local infusion of CGRP immediately following endothelin-1 challenge had no such protective actions, and significantly exacerbated the microvascular leakage and tissue injury at the higher dose. These studies suggest that CGRP can exert both pro- and anti-inflammatory actions in the gastric microcirculation.
Lopez-Belmonte
J
J
Wellcome Foundation Ltd., Beckenham, Kent, UK.
Whittle
B J
BJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D016232:Endothelins / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016232:Endothelins; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide