Effects of chronic infusion of (-)-isoprenaline on rat cardiac muscarinic (M2)-cholinoceptors and beta 1- and beta 2-adrenoceptors.

Abstract

1. The effects of chronic (-)-isoprenaline infusion (400 micrograms kg-1 h-1; 4 h-14 days) on rat ventricular muscarinic M2-cholinoceptors and beta 1- and beta 2-adrenoceptors was determined. [3H]-N-methylscopolamine (NMS) was used to measure M2-cholinoceptor binding and (-)-[125I]-cyanopindolol (CYP) was used for beta 1- and beta 2-adrenoceptor binding. 2. Chronic infusion of (-)-isoprenaline did not affect either the affinity of [3H]-NMS for M2-cholinoceptors, or the maximal density of these receptors (Bmax) at all treatment periods investigated (4 and 20 h; 7 and 14 days). The affinity of (-)-[125I]-CYP for beta-adrenoceptors was not changed following chronic (-)-isoprenaline infusion (4, 12 and 20 hours; 7 and 14 days). 3. Competition between (-)-[125I]-CYP and the selective beta 1-adrenoceptor antagonist CGP 20712A resulted in biphasic curves at all treatment periods corresponding to the presence of beta 1- and beta 2-adrenoceptor binding sites. beta 1-adrenoceptors made up the greater proportion of beta-adrenoceptors in rat ventricle. There was no change in the ratio of beta 1- to beta 2-adrenoceptors following 4 h (-)-isoprenaline infusion [(beta 1:beta 2), vehicle: 77.5 +/- 4.0%:22.5 +/- 4.0%, n = 6; (-)-isoprenaline: 79.2 +/- 1.2%:20.8 +/- 1.2%, n = 6], however infusion for 12 h increased the ratio [(beta 1:beta 2), vehicle: 65.2 +/- 6.1%:34.8 +/- 6.1%, n = 6; (-)-isoprenaline: 85.6 +/- 1.8%:14.4 +/- 1.8%, n = 6, P < 0.05], which was maintained for longer infusion periods (20 h-14 days). 4. Both beta 1- and beta 2-adrenoceptors were down-regulated in rat ventricular tissue following (-)-isoprenaline infusion. beta 2-adrenoceptors were down-regulated by 12 h (vehicle: 11.8 +/- 2.4 fmol mg protein-1, n = 6; (-)-isoprenaline: 3.5 +/- 0.4 fmol mg protein-1, n = 6, P < 0.05) however beta 1-adrenoceptors were not affected (vehicle: 21.7 +/- 2.0 fmol mg protein-1, n = 6; (-)-isoprenaline: 20.9 +/- 0.6 fmol mg protein-1, n = 6, P > 0.05) until 20 h infusion (vehicle: 19.4 +/- 2.2 fmol mg protein-1, n = 6; (-)-isoprenaline: 12.6 +/- 2.2 fmol mg protein-1, n = 6, P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)