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.

Abstract

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.

• Authors: M Hitchcock
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 71 Issue 1 Pg. 65-73 ( 1980) ISSN: 0007-1188 [Print] England
• PMID: 6162498 (Publication Type: Journal Article)

Chemical References

• Antigens
• Indoles
• Prostaglandins
• Pyridines
• SRS-A
• Oxidoreductases
• Thromboxane-A Synthase
• nictindole
• Indomethacin

Topics

• Airway Resistance (drug effects)
• Animals
• Antigens
• Guinea Pigs
• Histamine Release (drug effects)
• In Vitro Techniques
• Indoles (pharmacology)
• Indomethacin (pharmacology)
• Lung (drug effects, immunology, metabolism)
• Male
• Oxidoreductases (antagonists & inhibitors)
• Prostaglandins (metabolism)
• Pyridines (pharmacology)
• SRS-A (metabolism)
• Thromboxane-A Synthase (antagonists & inhibitors)
• Trachea (metabolism)