Modulation by opioids and by afferent sensory neurones of prostanoid protection of the rat gastric mucosa.
1. Pretreatment with capsaicin, to deplete sensory neuropeptides from primary afferent neurones or the administration of morphine (9 mg kg-1, i.v.), which can inhibit neuropeptide release, augmented gastric mucosal injury induced by a 5 min challenge with intragastric ethanol in the rat, as assessed by macroscopic and histological evaluation. 2. Morphine administration substantially attenuated the protective actions of the prostaglandin analogue 16,16 dimethyl prostaglandin E2 (dm PGE2; 0.5-20 micrograms kg-1, p.o.) against ethanol-induced damage. This reduced degree of protection by dmPGE2 was not however, the consequence of the enhanced level of damage. 3. These actions of morphine in reducing prostaglandin protection against mucosal injury were abolished by pretreatment (5 min) with naloxone (1 mg kg-1, i.v.) or the peripherally acting opioid antagonist, N-methyl nalorphine (6 mg kg-1, i.v.). 4. Capsaicin pretreatment (2 weeks before study), likewise attenuated the protective actions of dmPGE2, although to a lesser degree than did morphine. 5. These findings, thus implicate the involvement of capsaicin- and opioid-sensitive afferent neurones in the processes by which exogenous prostanoids can protect the gastric mucosa from damage.
Esplugues
J V
JV
Department of Pharmacology, University of Valencia, Spain.
Whittle
B J
BJ
Moncada
S
S
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009294:Narcotics; D011453:Prostaglandins; D009270:Naloxone; D000431:Ethanol; D009020:Morphine; D015232:Dinoprostone; D002211:Capsaicin