Characterization of alpha 1 D-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 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 microM 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 alpha 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.
Deng
X F
XF
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Chemtob
S
S
Varma
D R
DR
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000648:ultrastructure*; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000648:ultrastructure; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000502:physiology*; D012469:Salivary Glands / Q000648:ultrastructure; D013154:Spleen / Q000187:drug effects / Q000648:ultrastructure; D014316:Tritium; D014649:Vas Deferens / Q000187:drug effects / Q000648:ultrastructure
C547721:Adra1d protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D002316:Cardiotonic Agents; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D014316:Tritium; D010656:Phenylephrine; C053428:BMY 7378; D011224:Prazosin