Functional characterization of β-adrenoceptor subtypes in rabbit right atria

Abstract

The advent of radioligand binding studies has allowed the classification of receptor subtypes in various tissues. However, the presence of a receptor subtype in a heterogenous tissue does not insure that the receptor has a significant physiological role. β 1- and β 2-Adrenoceptors have been reported to coexist in the rabbit right atria. The purpose of the present investigation was to determine the physiological role of β-adrenoceptor subtypes in catecholamine-induced chronotropic responses in the rabbit right atria through comparison of data from functional and radioligand binding studies. Rank order of potency was determined using isoproterenol, epinephrine and norepinephrine for both chronotropic and inotropic responses in the rabbit right atria and right ventricular papillary muscles, respectively. These studies indicated that the β 1-adrenoceptor was primarily responsible for catecholamine-induced responses. Next, the β 1-selective antagonist, atenolol, was found to inhibit the chronotropic responses of the nonselective β-agonist, isoproterenol, and the β 2-selective agonist, terbutaline, to the same extent. These data indicate that terbutaline produces its chronotropic effects in the rabbit right atria through stimulation of β 1-, not β 2-adrenoceptors. Finally, competition studies for [ 125I] iodocyanopindolol and the relatively selective β 1- and β 2-adrenoceptor antagonists (ICI 89406 and ICI 118551, respectively) indicated that the ratio of β 1- to β 2-adrenoceptor subtypes is 6:1. It is concluded that while both receptors may be present in the rabbit right atria, the β 1-adrenoceptor is the predominant subtype both in density and physiological significance, while the β 2-adrenoceptor plays little, if any role, in the chronotropic responses induced by catecholamines.