Extracellular Ca(2+) entry and mobilization of inositol trisphosphate-dependent Ca(2+) stores modulate histamine and electrical field stimulation induced contractions of the guinea-pig prostate

Pharmacol Res. 2011 Sep;64(3):235-41. doi: 10.1016/j.phrs.2011.04.009. Epub 2011 Apr 25.

Abstract

This investigation aimed to examine the source of Ca(2+) mobilization that leads to the contractile response to either exogenously added histamine (1 μM-1mM) or electrical field stimulation (10Hz, 0.5ms, 60V). Removal of extracellular Ca(2+) by removal of Ca(2+) from the bathing medium reduced histamine (1mM) induced responses by 34% and responses induced by electrical field stimulation by 94%. Similarly, blockade of L-type Ca(2+) channels by nifedipine (1 μM) reduced histamine (1mM) induced responses by 43% and responses induced by electrical field stimulation by 77%. Application of cyclopiazonic acid (CPA) (10 μM) to inhibit Ca(2+) reuptake to the sarcoplasmic reticulum enhanced both histamine-induced and electrical field stimulation induced responses to a small degree, while the addition of the inosotol triphosphate (IP(3)) receptor antagonist, 2-aminophenoxyethane borane (2-APB) (100 μM) inhibited histamine induced responses by 70% and electrical field stimulation induced responses by 57%. Ryanodine (1 μM) did not affect contractile responses to either histamine or electrical field stimulation, either in the absence or presence of 2-APB (100 μM). During both histamine and electrical field stimulation induced contractions, prostate smooth muscle generates IP(3) receptor mediated Ca(2+) release in conjunction with Ca(2+) entry from the extracellular environment. Ryanodine receptors on the other hand, appear not to play a role in this physiological mechanism.

MeSH terms

  • Animals
  • Boranes / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Electric Stimulation
  • Guinea Pigs
  • Histamine / pharmacology*
  • Indoles / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Male
  • Muscle Contraction / drug effects*
  • Nifedipine / pharmacology
  • Prostate / metabolism
  • Prostate / physiology*
  • Ryanodine / pharmacology

Substances

  • Boranes
  • Calcium Channel Blockers
  • Indoles
  • Ryanodine
  • Histamine
  • Inositol 1,4,5-Trisphosphate
  • Calcium-Transporting ATPases
  • Nifedipine
  • Calcium
  • cyclopiazonic acid