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Eur J Pharmacol. 1995 Jan 5;272(1):1-11.

Epithelium-derived inhibitory prostaglandins modulate human bronchial smooth muscle responses to histamine.

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  • 1Asthma and Allergy Research Unit, University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia.

Abstract

The role of the bronchial epithelium and inhibitory prostaglandins in the induction of histamine tachyphylaxis in human isolated bronchial smooth muscle was investigated using bronchi obtained from 14 patients who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for > 2 months and from 14 untreated patients. Epithelium-intact bronchial strips from untreated patients demonstrated tachyphylaxis to histamine with the maximum response (Emax) reduced by 30 +/- 5% (P < 0.02) and the EC50 increased 1.86-fold (P < 0.02). Tachyphylaxis was not observed in epithelium-denuded strips. In epithelium-intact bronchial preparations from NSAID treated patients, the mean initial maximum tension generated in response to histamine was significantly greater than that for bronchial preparations from untreated patients (P < 0.05). In NSAID-treated patients, both epithelium-intact and denuded preparations failed to demonstrate tachyphylaxis. The generation of prostaglandin E2 and prostacyclin was assessed by radio-immunoassay using bronchi from untreated patients (n = 8). In epithelium-intact bronchial preparations, the generation of both prostaglandin E2 and prostacyclin was significantly increased by histamine exposure (P < 0.05) and was completely inhibited by indomethacin. However, the selective histamine H2 receptor antagonist, ranitidine, selectively inhibited the synthesis of prostaglandin E2 alone. Production of both prostaglandins was not altered by exposure to acetylcholine. These results suggest that prostaglandin E2 and prostacyclin are released primarily from the epithelium in response to histamine and may be specifically involved in inhibiting human bronchial smooth muscle responsiveness to this mediator. Significantly, the release of prostaglandin E2 appears to be selectively controlled by histamine H2 receptors, resident on the epithelium.

PMID:
7713139
[PubMed - indexed for MEDLINE]
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