ROLE OF INTRACELLULAR CA2+ STORES IN SMOOTH-MUSCLE CONTRACTIONS OF THE GUINEA-PIG VAS-DEFERENS

Guinea pig vas deferens was used as an animal model for alpha-1 adrenoceptor (alpha1-receptor) mediated contractions in human hyperplastic prostatic tissue. The selective alpha1-receptor agonist, phenylephrine (PE), induced fully reversible, dose-dependent contractions antagonized by increasing concentrations of the alpha1-receptor blockers prazosin (1-100 nM) and YM 617 (0.1-10 nM). Removal of extracellular Ca2+ reduced PE-evoked contractions in a time-dependent manner. Nifedipine 1-1000 nM), a blocker of voltage-dependent L-type Ca2+ channels (VDCC), inhibited the PE-induced response by up to 65%. Removal of extracellular Ca2+ abolished the alpha1-agonist reactivity in a time-dependent fashion. To elucidate the participation of intracellular Ca2+ stores in alpha1-receptor-mediated contractions, the tissue was pretreated with ryanodine (10 muM) or thapsigargin (0.1 muM), established inhibitors of Ca2+ release from intracellular pools. Both substances reduced the PE contractions by up to 80%. Nifedipine suppressed the remaining contractions completely. This provides evidence that Ca2+ influx through VDCC and Ca2+ release from intracellular stores contribute to alpha1-receptor-mediated contractions in the guinea pig vas deferens and may be important in obstructive benign prostatic hyperplasia.