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Interactions between the vascular peptide endothelin‐1 and sensory neuropeptides in gastric mucosal injury
Author(s) -
Whittle B.J.R.,
LopezBelmonte J.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12282.x
Subject(s) - neuropeptide , calcitonin gene related peptide , capsaicin , (+) naloxone , substance p , endothelin receptor , endogeny , medicine , endothelin 1 , endocrinology , pharmacology , endogenous opioid , neuropeptide y receptor , opioid peptide , chemistry , opioid , receptor
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 α‐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.