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 (a₁-receptor) mediated contractions in human hyperplastic prostatic tissue. The selective a₁-receptor agonist, phenylephrine (PE), induced fully reversible, dose-dependent contractions antagonized by increasing concentrations of the a₁-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 a₁-agonist reactivity in a time-dependent fashion. To elucidate the participation of intracellular Ca²⁺ stores in a₁-receptor contractions, the tissue was pretreated with ryanodine (10 µM) or thapsigargin (0.1 µM), 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 a₁-receptor contractions in the guinea pig vas deferens and may be important in obstructive benign prostatic hyperplasia.