Stimulation of P2y purinoceptors induces, via nitric oxide production, endothelium-dependent relaxation of human isolated corpus cavernosum

J Urol. 1999 Mar;161(3):955-9.

Abstract

Purpose: Endothelial P2y purinoceptor stimulation is known to induce vasodilatation mediated by NO release from endothelial cells. We examined the effect of a potent P2y agonist, adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS), on human corporal cavernosal strips and its dependence on a functional endothelial lining.

Materials and methods: The preparations mounted in isometric conditions were precontracted by noradrenaline (NA) at a concentration of 0.1 microM. Increasing concentrations of ADPbetaS from 1 microM to 100 microM were added in the presence and absence of a functional endothelium or in the presence and absence of an NO synthase inhibitor and a selective P2y antagonist. Acetylcholine (Ach)-induced relaxation was used in each experiment for control.

Results: In human precontracted corporal cavernosal strips with a functional endothelium (relaxed by acetylcholine) ADPbetaS induces a dose-dependent relaxation with maximal relaxation of 45.5+/-5.0% and an EC50 of 11.7 microM. The relaxant effect of ADPbetaS was reduced by 77.1+/-7.0% by reactive blue 2 (20 microM)(a P2y antagonist). L-NAME (L-Nitro Arginin Methyl Ester), an NO synthase inhibitor (100 microM), reduced Ach- and ADPbetaS- induced relaxations by 86.59+/-3.24% and 86.83+/-0.5% respectively. Ach- and ADPbetaS- induced relaxations were significantly inhibited after dislodging of the endothelial lining of the corporal cavernosal strips, 90.11+/-6.2% and 87.1+/-5% respectively.

Conclusions: Human corporal cavernosal strips can be relaxed by stimulation of P2y purinoceptors via NO release. This relaxation is an endothelium-dependent mechanism. Purines may be implicated in physiological erection in man.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives
  • Adenosine Diphosphate / pharmacology
  • Adult
  • Aged
  • Endothelium / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Muscle Relaxation / physiology*
  • Nitric Oxide / biosynthesis*
  • Norepinephrine / pharmacology
  • Penis / physiology*
  • Receptors, Purinergic P2 / physiology*
  • Thionucleotides / pharmacology

Substances

  • Receptors, Purinergic P2
  • Thionucleotides
  • Nitric Oxide
  • adenosine 5'-O-(2-thiodiphosphate)
  • Adenosine Diphosphate
  • Norepinephrine