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Stimulation of the antigen-induced contraction of guinea-pig trachea and immunological release of histamine and SRS-A from sensitized guinea-pig lung by (2-isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin



Stimulation of the antigen-induced contraction of guinea-pig trachea and immunological release of histamine and SRS-A from sensitized guinea-pig lung by (2-isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin



British Journal of Pharmacology 71(1): 65-73



1 (2-Isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin reduced basal tension and enhanced the antigen- and histamine-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. The stimulating effect of L8027 required the presence of the drug, while that of indomethacin persisted after its removal from the organ bath. 2 L8027 and indomethacin stimulated the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) and inhibited the de novo synthesis and release of malondialdehyde from actively sensitized guinea-pig lung fragments. 3 L8027 was 2,800 times more potent than indomethacin in both in vitro models of anaphylaxis. 4 A selective antagonist of SRS-A (FPL 55712) inhibited contractions produced by antigen, but had no effect on contractions produced by histamine. 5 Prostaglandins E and F2 alpha were continuously released into the organ bath fluid by the resting trachea. Contractions induced by antigen or histamine increased the rate of prostaglandin efflux. 6 L8027 had no effect on the efflux of prostaglandins E and F2 alpha at rest and during contraction. Indomethacin inhibited prostaglandin efflux at rest and during contraction while present in the organ bath. Prostaglandin efflux was restored to 80% of control after removal of indomethacin. 7 The results suggest that prostaglandins E and F2 alpha have no role in the stimulation by L8027 and indomethacin of the contractile responses of guinea-pig trachea. The possible mechanism for the effects of these drugs is discussed.

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Accession: 044404205

Download citation: RISBibTeXText

PMID: 6162498

DOI: 10.1111/j.1476-5381.1980.tb10910.x


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