Characterization of alpha 1-adrenoceptor subtypes in tension response of human prostate to electrical field stimulation

Br J Pharmacol. 1995 May;115(1):142-6. doi: 10.1111/j.1476-5381.1995.tb16331.x.

Abstract

1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical field stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked these effects by only 50%. 3. The contractile responses of rat vas deferens and spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha 1A-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical field stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 microM), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5. The involvement of prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined. Clonidine (3 x 10-9 to 3 x 10- M) blocked concentration-dependently the contractile response to electrical field stimulation of human prostate and this inhibitory effect was reversed by yohimbine (10-7 M). Additionally, the inhibitory effect of CEC (3 x 10-6 to 3 x 10-4 M)to the nerve-mediated contraction was also partially reversed by yohimbine (10-7 M).6. It is suggested that the putative czA-adrenoceptors in human prostate may be functionally confined to the synaptic region whereas only minor populations of the putative alpha 1B- and/or alpha 1c-adrenoceptors exist in this region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / pharmacology
  • Animals
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Electric Stimulation
  • Humans
  • Hyperplasia / metabolism*
  • In Vitro Techniques
  • Isometric Contraction
  • Male
  • Muscle, Smooth / metabolism
  • Nifedipine / pharmacology
  • Piperazines / pharmacology
  • Prazosin / pharmacology
  • Prostate / metabolism*
  • Rats
  • Receptors, Adrenergic, alpha-1 / classification*
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Spleen / drug effects
  • Spleen / metabolism
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism
  • Yohimbine / pharmacology

Substances

  • Adrenergic Antagonists
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • 5-methylurapidil
  • Yohimbine
  • chlorethylclonidine
  • Nifedipine
  • Clonidine
  • Prazosin