Local opioid-sensitive afferent sensory neurones in the modulation of gastric damage induced by Paf.
1. The role of local sensory neurones in modulating the extent of gastric mucosal damage induced by close-arterial infusion of platelet-activating factor (Paf 50 ng kg-1 min-1 for 10 min) has been investigated in the anaesthetized rat. 2. Local intra-arterial infusion of the neurotoxin, tetrodotoxin (TTX), substantially augmented the mucosal damage induced by Paf, as assessed by both macroscopic and histological techniques. 3. In rats pretreated with capsaicin 2 weeks prior to study, to induce a functional ablation of primary afferent neurones, gastric damage induced by Paf was significantly augmented. 4. Administration of morphine (0.75-3 mg kg-1 i.v.) or its peripherally acting quaternary analogue, N-methyl morphine (15 mg kg-1 i.v.), also significantly enhanced the gastric damage induced by Paf. 5. The potentiation by morphine of Paf-induced gastric damage was inhibited by administration of the opioid antagonists, naloxone (1 mg kg-1 i.v.) or the peripherally acting N-methyl nalorphine (3 mg kg-1 i.v.). 6. Administration of TTX or morphine alone, or pretreatment with capsaicin did not induce any detectable mucosal damage, suggesting that interference with local sensory neuronal activity itself does not directly induce mucosal disruption. 7. These results indicate that peripheral opiate-sensitive afferent sensory neurones play a physiological defensive role in the mucosa, attenuating the extent of gastric damage induced by Paf.
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
J V
JV
Esplugues
B J
BJ
Whittle
S
S
Moncada
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects*; D010972:Platelet Activating Factor; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology
D009294:Narcotics; D010972:Platelet Activating Factor; D013779:Tetrodotoxin; D009020:Morphine; D002211:Capsaicin