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 (alpha 1-receptor) mediated contractions in human hyperplastic prostatic tissue. The selective alpha 1-receptor agonist, phenylephrine (PE), induced fully reversible, dose-dependent contractions antagonized by increasing concentrations of the alpha 1-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 alpha 1-agonist reactivity in a time-dependent fashion. To elucidate the participation of intracellular Ca2+ stores in alpha 1-receptor-mediated contractions, the tissue was pretreated with ryanodine (10 microM) or thapsigargin (0.1 microM), 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 alpha 1-receptor-mediated contractions in the guinea pig vas deferens and may be important in obstructive benign prostatic hyperplasia.
Drescher
P
P
Urology Section, Veterans Hospital, Madison, WI.
Eckert
R E
RE
Madsen
P O
PO
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000503:physiopathology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D010656:Phenylephrine; D000077409:Tamsulosin; D009543:Nifedipine; D002118:Calcium; D011224:Prazosin