A Different Desensitization Pattern of Cardiac β-Adrenoceptor Subtypes by Prolonged In Vivo Infusion of Isoprenaline

Abstract

(–)Isoprenaline was continuously administered to rats at a rate of 0.4 mg/kg/h for 7 days via subcutaneously (s.c.) implanted osmotic minipumps. This treatment induced cardiac hypertrophy and a marked decrease in basal as well as catecholamine-stimulated adenylate cyclase activity in a ventricular plasma membrane fraction. The total number of (β-adrenoceptors was downregulated by one-half the amount of the receptor sites obtained in a control group. However, in the isoprenaline-treated group, the (β-adrenoceptors constituted a significantly smaller proportion of the total 4bT-adrenoceptor population (28%) than in the control group (50%). Transformation of these relative into absolute values indicates that prolonged isoprenaline treatment induced a significantly higher downregulation of β2- than of (β1-adrenoceptors. The fact of a different (β-adrenoceptor desensitization pattern in response to in vivo administration of nonselective β-adrenergic agonists therefore must be taken into consideration when desensitization is used as a method for determination of subtype selectivity of an agonist per se. However, we were unable to detect the “lost” (β-adrenoceptors in a light vesicular fraction. In our study, this fraction was not separable from plasma membranes, as substantiated by levels of plasma membrane markers as high as in the plasma membrane fraction and by a guanine nucleotide-dependent adenylate cyclase activity.