title: Mechanoinhibitory effect of estradiol in guinea pig urinary bladder smooth muscles.
abstract: The mechanoinhibitory effect of estradiol on the myogenic activity of guinea pig urinary bladder detrusor muscles was studied. In detrusor muscles tonically contracted with 80 mmol/lKCl, 17 beta-estradiol and the nonestrogenic isomer 17 alpha-estradiol at 30 mumol/l reduced the contraction by 64 +/- 3 and 59 +/- 1%, respectively. In detrusor muscles maintained in Ca(2+)-free media and depolarized with 80 mmol/lKCl, the contractile response of muscles to the reintroduction of Ca2+ was inhibited in a dose-dependent manner by 17 beta-estradiol, suggesting that 17 beta-estradiol blocked entry of extracellular Ca2+ into bladder smooth muscle cells and reduced the rise of intracellular Ca2+ required for contraction. In detrusor muscles mildly depolarized with 15 mmol/lKCl, 17 beta-estradiol reduced the myogenic activity with an IC50 of 6.8 +/- 1.3 mumol/l. The higher activity of 17 beta-estradiol in this latter test indicated that estradiol could also possess some K+ channel opening activity. Glibenclamide at 1 mumol/l did not affect the relaxant activity of 17 beta-estradiol in detrusor muscles stimulated with 15 mmol/l; however, this activity was diminished in a dose-dependent manner by iberiotoxin. Collectively, these results have demonstrated that in addition to the Ca2+ antagonist activity, 17 beta-estradiol possesses K+ channel opening activity in guinea pig urinary bladder smooth muscles, activating probably not the adenosine triphosphate sensitive, but the Ca(2+)-dependent large-conductance K+ channels.
authors.affiliation: Department of Pharmacology, Zeneca Pharmaceuticals Group, Zeneca Inc., Wilmington, DE 19897, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Yasay
authors.forename: S T
authors.initials: ST
authors.lastname: Kau
authors.forename: J H
authors.initials: JH
authors.lastname: Li
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D010455:Peptides; D015221:Potassium Channels; D004958:Estradiol; C064719:iberiotoxin; D000255:Adenosine Triphosphate; D005905:Glyburide