Regional differences of beta 1- and beta 2-adrenoceptor-mediated functions in feline heart. A beta 2-adrenoceptor-mediated positive inotropic effect possibly unrelated to cyclic AMP

Abstract

The effects of (-)-adrenaline and (-)-noradrenaline were studied on isolated preparations of kitten heart. To define the contribution of beta 1-adrenoceptors (beta 1AR) and beta 2-adrenoceptors (beta 2AR) we used as tools the highly beta 1AR-selective antagonist CGP 20,712 A and non-linear analysis of antagonism. The beta 2AR-mediated responses to the catecholamines, disclosed by CGP 20,712 A, were verified by blockade with the beta 2AR-selective ICI 118,551. The relative density and contribution of beta 1AR and beta 2AR to (-)-adrenaline- and (-)-noradrenaline-induced adenylyl cyclase stimulation was also estimated in right ventricular membranes. 1. In the sinoatrial pacemaker (-)-adrenaline caused positive chronotropic effects through both beta 1AR and beta 2AR while (-)-noradrenaline does so predominantly through beta 1AR. During beta 1AR blockade (-)-adrenaline did cause the same maximum effects through beta 2AR as (-)-noradrenaline did through beta 1AR. 2. In left atria (-)-adrenaline caused positive inotropic effects predominantly through beta 1AR. CGP 20,712 A also uncovered a beta 2AR component at high (-)-adrenaline concentrations comprising one third of the maximum beta 1AR-mediated response. 3. Receptor binding assays revealed that 80% of right ventricular beta AR were beta 1AR and 20% beta 2AR. Consistent with this finding, around 80% of the adenylyl cyclase stimulation by both (-)-noradrenaline and (-)-adrenaline was mediated through beta 1AR, around 20% through beta 2AR. The positive inotropic effects of (-)-noradrenaline appeared to be nearly exclusively mediated through beta 1AR in right ventricular papillary muscles. 4. The positive inotropic effects of (-)-adrenaline were quite variable with regard to beta 1AR and beta 2AR in right ventricular papillary muscles. Although beta 1AR-mediated effects are predominant in many muscles with only a small contribution of beta 2AR, in some muscles beta 2AR mediated around 50% of the maximum effect elicited through beta 1AR. In 3 out of 17 muscles beta 2AR mediated the same maximum effect of (-)-adrenaline as beta 1AR. 5. On occasion, we found marked beta AR heterogeneity amongst two muscles from the same right ventricle. One muscle only exhibited beta 1AR-mediated effects of (-)-adrenaline whereas in the other muscle maximal effects could be elicited through beta 2AR.(ABSTRACT TRUNCATED AT 400 WORDS)