The role of alpha1D-adrenoceptors in prostatic contraction examined using protection studies.
1 The aim of the study was to investigate the role of the alpha1D-adrenoceptor in alpha1-adrenoceptor-induced contraction of human prostate by means of protection experiments. 2 Responses of human prostate strips to noradrenaline were recorded, along with responses of rat aorta and vas deferens, tissues possessing predominantly alpha1D- and alpha1A-adrenoceptors respectively, for comparison. alpha1-adrenoceptors were then inactivated by incubation with the irreversible antagonist phenoxybenzamine. In some tissues alpha1A- or alpha1D-adrenoceptors were 'protected' from inactivation by incubation in the presence of the selective alpha1A- or 1D-adrenoceptor antagonists 5-methylurapidil and BMY 7378 before recording further responses to noradrenaline. 3 Phenoxybenzamine reduced the maximum noradrenaline-induced response and the potency of noradrenaline in all tissues. In rat vas deferens and human prostate, 5-methylurapidil protected alpha1A-adrenoceptors in a concentration-dependent manner. In rat aorta, 10 nM BMY 7378 almost fully protected alpha1D-adrenoceptors. However, concentrations of BMY 7378 up to 30-fold higher failed to protect receptors in the human prostate. 4 These results suggest that in human prostate functional alpha1D-adrenoceptors do not contribute to noradrenaline-induced contractile responses.
Chess-Williams
R
R
Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, UK.
Mason
S
S
Sellers
D J
DJ
Wyllie
M
M
Chapple
C R
CR
D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014649:Vas Deferens / Q000187:drug effects
C547719:ADRA1D protein, human; C547721:Adra1d protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000477:Alkylating Agents; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D010643:Phenoxybenzamine; C057446:5-methylurapidil; C053428:BMY 7378; D009638:Norepinephrine