Mechanoinhibitory effect of estradiol in guinea pig urinary bladder smooth muscles.
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.
Yasay
G D
GD
Department of Pharmacology, Zeneca Pharmaceuticals Group, Zeneca Inc., Wilmington, DE 19897, USA.
Kau
S T
ST
Li
J H
JH
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
D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D010455:Peptides; D015221:Potassium Channels; D004958:Estradiol; C064719:iberiotoxin; D000255:Adenosine Triphosphate; D005905:Glyburide