Response of isolated guinea-pig tracheal muscle to glucocorticoid and non-glucocorticoid succinates.
Glucocorticoids have been reported to relax tracheal smooth muscle and to potentiate its response to isoproterenol. For this reason, isolated tracheal muscle has been studied as a model system for exploring some of the mechanisms of glucocorticoid action in the therapy of asthma. Various glucocorticoid succinates and phosphates were tested in guinea-pig tracheal muscle for relaxing activity ahd potentiation of the isoproterenol response. In both of these activities, the glucocorticoid succinates were more effective than the corresponding phosphates. There were no differences in potency among the glucocorticoids commensurate with their antiasthmatic activity. In comparing the succinate derivatives of glucocorticoids with non-glucocortiocod succinates, it was found that while 10(-3) M glucocorticoid succinate was required to demonstrate relaxation, the non-glucocorticoids were capable of producing complete relaxation at 10(-3) M and demonstrable relaxation at 10(-4) M. The latter were also capable of potentiating the isoproterenol response at a dose of 10(-4) M. It apears that these responses to glucocorticoids are due to the succinate derivative form of the steroid and not to the glucocorticoid itself. This wound suggest that glucocorticoid succinate relaxation and its isoproterenol potentiation in tracheal muscle does not provide an apropriate model for studying the mechanisms of the antiasthmatic effect of glucocorticoids.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D005938:Glucocorticoids; D006634:Histamine H1 Antagonists; D013386:Succinates; D007545:Isoproterenol