Characterization of α(1D)-adrenoceptor subtype in rat myocardium, aorta and other tissues

Abstract

1. This study was done to characterize the functional role of α(1D)-adrenoceptors in rat myocardium, aorta, spleen, vas deferens and prostate by use of the selective antagonist BMY 7378. 2. BMY 7378 inhibited [3H]-prazosin binding to aortic membranes with a potency (pK(i) 9.8 ± 0.40) approximately 100 fold higher than in right ventricular membranes (pK(i) 7.47 ± 0.11) and approximately 1000 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 (6.58 ± 0.06). 3. BMY 7378 antagonized the positive inotropic effects of phenylephrine (in the presence of 1 μM propranolol) on right ventricles (pA2 7.0 ± 0.11), left atria (pK(B) 7.04 ± 0.18) and papillary muscles (pK(B) 6.9 ± 0.1) and inhibited phenylephrine-induced increase in inositol phosphates. 4. BMY 7378 was approximately 100 fold more potent as an antagonist of phenylephrine on aortic strips (pA2 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 suppressed the maximal effects of phenylephrine on spleen; 5-methylurapidil antagonized the effects of phenylephrine on aortic strips (pA2 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 decrease in mean blood pressure of urethane-anaesthetized rats and its hypotensive efficacy was equal to that of hexamethonium. 7. The data suggest that α(1D)-adrenoceptors play a significant role in rat aorta, a minor role in the heart, vas deferens and spleen and virtually no role in the prostate.