Esplugues J V, Whittle B J
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Am J Physiol. 1989 Feb;256(2 Pt 1):G275-82. doi: 10.1152/ajpgi.1989.256.2.G275.
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.
血小板活化因子（PAF）可能参与了胃肠道损伤和动力变化的病理生理过程。现已在戊巴比妥钠麻醉的大鼠中确定了PAF在体内诱导胃收缩的作用。局部动脉内输注PAF（5 - 50 ng·kg⁻¹·min⁻¹，持续10分钟）可使胃内压持续升高，随后在输注后进一步升高。类花生酸生物合成抑制剂对这些胃动力变化没有影响。然而，西咪替丁或甲基麦角新碱预处理可使胃内压的初始升高降低50%，而美吡拉敏、肾上腺素α和β受体阻断剂、阿托品、六甲铵或迷走神经切断术则没有影响。在局部输注河豚毒素期间，胃内压的初始升高未能维持，输注后升高消失。使用这些抑制剂和拮抗剂时，PAF诱导的黏膜损伤程度与胃内压升高之间没有一致的相关性。河豚毒素对血栓素模拟物U - 46619诱导的胃内压变化没有影响。静脉注射大肠杆菌和伤寒沙门氏菌内毒素（50 mg/kg）也会使胃内压升高，在10分钟后达到峰值，随后缓慢下降。这些作用被特异性PAF受体拮抗剂L652,731抑制，表明内源性PAF释放可能促成内毒素诱导的胃动力增加。本研究表明，PAF最初直接作用于平滑肌，并通过组胺和5 - 羟色胺释放，由于非肾上腺素能非胆碱能神经元活动的激活而产生继发性动力反应。
