title: 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.
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.
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lam
authors.forename: Karen
authors.initials: K
authors.lastname: Kerr
authors.forename: Sabatino
authors.initials: S
authors.lastname: Ventura
authors.forename: Betty
authors.initials: B
authors.lastname: Exintaris
mesh_terms: D000818:Animals; D001880:Boranes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D011467:Prostate / Q000378:metabolism / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology
chemical_list: D001880:Boranes; D002121:Calcium Channel Blockers; D007211:Indoles; D012433:Ryanodine; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid