ALPHA(1)-ADRENOCEPTOR MEDIATED ACTIVATION OF NA K/2CL COTRANSPORT ANDK+ CHANNELS IN THE RAT-HEART INVOLVES DIFFERENT RECEPTOR SUBTYPES/

Involvement of receptor subtypes in the alpha(1)-adrenoceptor mediated activation of Na/K/2Cl-cotransport and K+ channels was studied in iso lated perfused spontaneously beating rat hearts stimulated by phenylep hrine (30 mu mol/l) in the presence of a beta-adrenoceptor antagonist (1 mu mol/l timolol). The effects of alpha(1)-adrenoceptor stimulation on K+ translocation mechanisms were. studied by measuring the efflux of Rb-86(+) (a potassium analogue). The effects of 50 mu mol/l bumetan ide (Na/K/2Cl-cotransport inhibitor) and 0.1-0.3 mmol/14-aminopyridine (inhibitor of K+ channels) were studied in the presence of alpha(1)-a drenoceptor subtype selective antagonists. Bumetanide reduced the alph a(1)-adrenoceptor mediated increase in Rb-86(+) efflux by 53 +/- 16.4 % (n=14, P<0.001) in hearts pretreated with the preferentially alpha(1 B)-adrenoceptor antagonist chloroethylclonidine (CEC, 10 mu mol/l), an d by 35 +/- 7.3 % (n=15, P<0.001) in the presence of the preferentiall y alpha(1D)-adrenoceptor antagonist BMY 7378 (1 mu mol/l). In the pres ence of the preferentially alpha(1A)-adrenoceptor antagonist 5-methylu rapidil (10 mu mol/l), however, bumetanide had no effect on the respon se to phenylephrine. 4-Aminopyridine reduced the phenylephrine stimula ted Rb-86(+) efflux in the presence of 5-methylurapidil, but the effec t of the K+-channel blocker was eliminated in CEC treated hearts. Thus the effects of the two translocation inhibitors were influenced diffe rently by the two subtype selective antagonists, showing that alpha(1) -adrenoceptor stimulation activates a bumetanide sensitive Na/K/2Cl-co transport mechanism in the rat heart mainly through the alpha(1A)- rec eptor subtype while the 4-aminopyridine sensitive K+ channels, are mai nly activated by the alpha(1B)-adrenoceptor subtype.