Terbutaline-induced desensitization in rabbit aorta in vitro.
In vivo administration of terbutaline, a beta 2-adrenergic agonist, desensitizes beta-adrenergic agonist-induced responses in isolated rabbit aorta. Characteristics of the desensitization following in vitro application of terbutaline and prevention of such desensitization by certain agents were studied. Endothelium-denuded rabbit aorta rings were incubated with 10 or 50 microM terbutaline for 30 or 60 min, or with no drug as a control. Following contraction with 1 microM phenylephrine, relaxations to cumulative concentrations of isoproterenol were determined. Rings exposed to terbutaline relaxed less to isoproterenol, indicating desensitization of beta-adrenergic receptors. The desensitization was homologous, exposure time- and concentration-dependent, and at least partially reversible. It does not require extracellular calcium to develop and is not blocked by verapamil, ketotifen, prednisolone or nedocromil. Thus, terbutaline-induced desensitization occurs in vitro, is homologous, does not require calcium, and is not blocked by the four compounds tested.
Hsu
C H
CH
College of Pharmacy, University of Oklahoma, Health Sciences Center, Oklahoma City 73190.
Robinson
C P
CP
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D017835:Nedocromil / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013726:Terbutaline / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D017835:Nedocromil; D010656:Phenylephrine; D011239:Prednisolone; D014700:Verapamil; D000241:Adenosine; D007545:Isoproterenol; D013726:Terbutaline; D002118:Calcium; D007665:Ketotifen