The Functional Role of the Coexistence of β ₁- and β ₂-Adrenoceptors in the Human Heart

Abstract

The subclassifìcation of β-adrenoceptors into the subtypes β ₁ and β ₂ was originally postulated by Lands et al. (1967 a, b), based on the findings that sympathomimetic agents evoked their effects on different tissues with different orders of potency. β ₁- and β ₂-Adrenoceptors differ in their relative affinities for the endogenous catecholamines noradrenaline and adrenaline. At β ₁ −adrenoceptors, which mediate cardiac effects and lipolysis, noradrenaline and adrenaline are equipotent; on the other hand, at β ₂-adrenoceptors, which mediate smooth muscle relaxation, adrenaline is approximately 10–30 times more potent than noradrenaline. During the past few years, growing evidence has accumulated that β ₁- and β ₂-adrenoceptors are not always organ-specifically distributed, but that both β-adrenoceptor subtypes can coexist in a single organ (for recent reviews, see Minneman et al. 1981; Stiles et al. 1984). This was first suggested in 1972 by Carlsson et al., who showed that equal submaximal chronotropic responses of the cat heart to β-adrenergic agonists were antagonized to a different extent by practolol (a β ₁-selective antagonist) and H 35/25 (a β ₂-selective antagonist). Subsequently, similar effects have been obtained in several in vivo and in vitro experiments in cat, dog and guinea pig hearts as well as in guinea pig and rabbit trachea (for references, see Daly and Levy 1979), thus supporting the concept of the coexistence of β ₁- and β₂-adrenoceptors in a single organ.