Mechanisms contributing to gastric motility changes induced by PAF-acether and endotoxin in rats.
Platelet-activating factor (PAF) may be involved in the pathophysiology of gastrointestinal damage and motility changes. The effects of PAF in inducing gastric contractions in vivo have now been determined in pentobarbital sodium-anesthetized rats. Local intra-arterial infusion of PAF (5-50 ng.kg-1.min-1 for 10 min) induced a maintained rise in intragastric pressure followed by a further postinfusion increase. Inhibitors of eicosanoid biosynthesis had no effect on these gastric motility changes. However, pretreatment with cimetidine or methysergide decreased by 50% the initial increase in intragastric pressure, whereas mepyramine, adrenergic alpha- and beta-receptor blockade, atropine, hexamethonium, or vagotomy had no effect. During the local infusion of tetrodotoxin, the initial increase in intragastric pressure was not maintained, and the postinfusion increase was abolished. With these inhibitors and antagonists, there was no consistent correlation between the extent of PAF-induced mucosal damage and increase in intragastric pressure. Tetrodotoxin had no effect on the changes in intragastric pressure induced by the thromboxane mimetic U-46619. Administration of Escherichia coli and Salmonella typhosa endotoxin (50 mg/kg iv) also increased intragastric pressure, which peaked after 10 min and slowly declined thereafter. These effects were inhibited by the specific PAF-receptor antagonist L652,731, suggesting that the endogenous release of PAF may contribute to the endotoxin-induced increases in gastric motility. The present study suggests that PAF initially acts directly on smooth muscle and through histamine and serotonin release with a secondary motility response due to activation of nonadrenergic noncholinergic, neuronal activity.
Esplugues
J V
JV
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Whittle
B J
BJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D005663:Furans / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011312:Pressure; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology*
D005663:Furans; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D013779:Tetrodotoxin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran