Identification of alpha1-adrenoceptor subtypes involved in contraction of young CD rat epididymal vas deferens

Eur J Pharmacol. 2009 Jan 14;602(2-3):388-94. doi: 10.1016/j.ejphar.2008.10.067. Epub 2008 Nov 14.

Abstract

Contraction of rat epididymal vas deferens is regulated via a release of neurotransmitters from autonomic nerves and is mediated by alpha(1)-adrenoceptors. This study was directed to the characterization of alpha(1)-adrenoceptors involved in the contraction of the epididymal portion of young CD rat vas deferens, that were selectively discriminated in two populations through the irreversible blockade of two beta-chloroethyamines, 1 and 2. The antagonist activity of known subtype-selective alpha(1)-adrenoceptor antagonists, WB4101, 5-MU, and RS17053 (alpha(1A)), (+)-cyclazosin (alpha(1B)), and BMY7378 (alpha(1D)), was evaluated in the alpha(1)-adrenoceptors of the studied tissue as such and after pre-treatment with a proper discriminating concentration of beta-chloroetylamines 1 and 2, comparing the results with the affinities determined in classical Wistar rat models: prostatic vas deferens (alpha(1A)), spleen (alpha(1B)), and thoracic aorta (alpha(1D)). The results suggested that two alpha(1A)-adrenoceptors are involved in the contraction of the epididymal vas deferens of young CD rats. These may represent two alpha(1A)-adrenoceptor isoforms that are selectively and irreversibly blocked by beta-chloroetylamines 1 and 2, and reversibly antagonized by RS17053. The minor population, preferentially blocked by 1, seems correspond to a classical alpha(1A)-adrenoceptor subtype, while the major population, preferentially blocked by 2 and antagonized by RS17053 with low affinity, seems to correspond to an alpha(1L)-adrenoceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists
  • Amines / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Epididymis / cytology
  • Epididymis / drug effects
  • Epididymis / metabolism*
  • Inhibitory Concentration 50
  • Male
  • Muscle Contraction / drug effects
  • Norepinephrine / pharmacology
  • Rats
  • Receptors, Adrenergic, alpha-1 / classification*
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Vas Deferens / cytology
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism*

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Amines
  • Receptors, Adrenergic, alpha-1
  • Norepinephrine