CHARACTERIZATION OF ALPHA(1D)-ADRENOCEPTOR SUBTYPE IN RAT MYOCARDIUM,AORTA AND OTHER TISSUES

1 This study was done to characterize the functional role of alpha(1D) -adrenoceptors in rat myocardium, aorta, spleen, vas deferens and pros tate by use of the selective antagonist BMY 7378. 2 BMY 7378 inhibited [H-3]-prazosin binding to aortic membranes with a potency (pK(i) 9.8/-0.40) approximately 100 fold higher than in right ventricular membra nes (pK(i) 7.47+/-0.11) and approximately 1,000 fold higher than that in plasma membranes of the prostate (pK(i) 6.62+/-0.39), vas deferens (pK(i) 6.67+/-0.15), salivary gland (pK(i) 6.46+/-0.38) and liver (6.5 8+/-0.06). 3 BMY 7378 antagonized the positive inotropic effects of ph enylephrine (in the presence of 1 mu M propranolol) on right ventricle s (pA(2) 7.0+/-0.11), left atria (pK(B) 7.04+/-0.18) and papillary mus cles (pK(B) 6.9+/-0.1) and inhibited phenylephrine-induced increase in inositol phosphates. 4 BMY 7378 was approximately 100 fold more poten t as an antagonist of phenylephrine on aortic strips (pA(2) 9.0+/-0.13 ) than on vas deferens (pK(B) 7.17+/-0.08) and spleen (pK(B) 7.16+/-0. 21); it was ineffective on the prostate. 5 Chloroethylclonidine suppre ssed the maximal effects of phenylephrine on spleen; 5-methylurapidil antagonized the effects of phenylephrine on aortic strips (pA(2) 7.98/-0.08), vas deferens (pK(B) 8.89+/-0.07) and prostate (pK(B) 8.85+/-0 .21). 6 BMY 7378 caused a dose (0.1-100 nmol kg(-1))-dependent decreas e in mean blood pressure of urethane-anaesthetized rats and its hypote nsive efficacy was equal to that of hexamethonium. 7 The data suggest that alpha(1D)-adrenoceptors play a significant role in rat aorta, a m inor role in the heart, vas deferens and spleen and virtually no role in the prostate.