The role of alpha1D-adrenoceptors in prostatic contraction examined using protection studies

Auton Autacoid Pharmacol. 2002 Oct-Dec;22(5-6):291-6. doi: 10.1046/j.1474-8673.2002.00272.x.

Abstract

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.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Alkylating Agents / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth, Vascular / drug effects
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / pharmacology
  • Phenoxybenzamine / pharmacology
  • Piperazines / pharmacology
  • Prostate / drug effects*
  • Rats
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Vas Deferens / drug effects

Substances

  • ADRA1D protein, human
  • Adra1d protein, rat
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Alkylating Agents
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • Phenoxybenzamine
  • 5-methylurapidil
  • BMY 7378
  • Norepinephrine