MECHANISM OF ISOPROTERENOL-INDUCED DESENSITIZATION OF TRACHEAL SMOOTH-MUSCLE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 203  (1) , 12-22
Abstract
Isolated rat tracheal smooth muscle became considerably less sensitive to the relaxing action of isoproterenol after being incubated with 5 .times. 10-6 M isoproterenol for 30 min. Pretreatment of the tissue with propranolol, but not with methylprednisolone, clearly reduced the isoproterenol-induced densensitization. This suggested that propranolol by occupying the .beta. adrenergic receptor prevented isoproterenol from binding to this receptor, thereby preventing the isoproterenol-induced desensitization. An isoproterenol-desensitized tracheal preparation exhibited a diminished sensitivity to other .beta. agonists, but not to the spasmolytic actions of D600 [.alpha.-isopropyl-.alpha.-[N-methyl-N-homoveratryl-.alpha.-aminopropyl]-3,4,5-trimethoxyphenyl-acetonitrile], hydralazine, sodium nitrite and aminophylline. The .beta. receptor is apparently specifically involved in the desensitization induced by isoproterenol. A highly desensitized tissue could always be made to undergo complete relaxation by exposing it to sufficiently high concentrations of isoproterenol. There appeared to be no positive indication of a very large change in the apparent intrinsic activity of the isoproterenol in the desensitized tissue. The dissociation constant for the propranolol .beta. receptor complex in the desensitized tissue was 180-fold larger than that in the normal tissue. These findings provide strong evidence that 1 demonstrable cellular change that occurs in the desensitized tissue is a pronounced reduction in the affinity of the .beta. receptors for isoproterenol.

This publication has 1 reference indexed in Scilit: