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.