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

Guinea pig vas deferens was used as an animal model for alpha-1 adreno ceptor (alpha1-receptor) mediated contractions in human hyperplastic p rostatic tissue. The selective alpha1-receptor agonist, phenylephrine (PE), induced fully reversible, dose-dependent contractions antagonize d by increasing concentrations of the alpha1-receptor blockers prazosi n (1-100 nM) and YM 617 (0.1-10 nM). Removal of extracellular Ca2+ red uced PE-evoked contractions in a time-dependent manner. Nifedipine 1-1 000 nM), a blocker of voltage-dependent L-type Ca2+ channels (VDCC), i nhibited the PE-induced response by up to 65%. Removal of extracellula r Ca2+ abolished the alpha1-agonist reactivity in a time-dependent fas hion. To elucidate the participation of intracellular Ca2+ stores in a lpha1-receptor-mediated contractions, the tissue was pretreated with r yanodine (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 contra ctions completely. This provides evidence that Ca2+ influx through VDC C and Ca2+ release from intracellular stores contribute to alpha1-rece ptor-mediated contractions in the guinea pig vas deferens and may be i mportant in obstructive benign prostatic hyperplasia.