Characterization of α1D‐adrenoceptor subtype in rat myocardium, aorta and other tissues

1 This study was done to characterize the functional role of α1D‐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 (pKi 9.8 ± 0.40) approximately 100 fold higher than in right ventricular membranes (pKi 7.47 ± 0.11) and approximately 1,000 fold higher than that in plasma membranes of the prostate (pKi 6.62 ± 0.39), vas deferens (pKi 6.67 ± 0.15), salivary gland (pKi 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 (pKB 7.04 ± 0.18) and papillary muscles (pKB 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 (pKB 7.17 ± 0.08) and spleen (pKB 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 (pKB 8.89 ± 0.07) and prostate (pKB 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 α1D‐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.

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