Interactions between the vascular peptide endothelin-1 and sensory neuropeptides in gastric mucosal injury.
1. The interactions between endogenous and exogenous sensory neuropeptides on gastric mucosal injury induced by endothelin-1 (ET-1) have been investigated in the anaesthetized rat. 2. Close intra-arterial infusion of ET-1 (4-20 pmol kg-1 min-1) dose-dependently induced vasocongestion and haemorrhagic necrosis in the gastric mucosa. 3. Capsaicin-pretreatment, two weeks earlier to deplete sensory neuropeptides from primary afferent neurones, augmented the mucosal damage induced by ET-1, as assessed by both macroscopic and histological examination. 4. The damage induced by threshold doses of ET-1 alone or in capsaicin-pretreated rats was further enhanced by administration of indomethacin (5 mg kg-1, i.v.), indicating a modulatory influence of endogenous prostanoids. 5. Morphine administration (3 mg kg-1, i.v.), which can prevent neuropeptide release, augmented the damage induced by threshold doses of ET-1, this effect being reversed by naloxone (1 mg kg-1, i.v.). 6. Concurrent local intra-arterial infusion of rat alpha-calcitonin gene-related peptide (10-50 pmol kg-1 min-1) dose-dependently reduced the mucosal injury induced by ET-1. 7. These findings suggest interactions between ET-1 and sensory neuropeptides, which may reflect an important influence of these peptide mediators in the regulation of mucosal integrity.
Whittle
B J
BJ
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
Lopez-Belmonte
J
J
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009479:Neuropeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology
D016232:Endothelins; D009479:Neuropeptides; D009020:Morphine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D007213:Indomethacin