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/l KCl, 17β-estradiol and the nonestrogenic isomer 17α-estradiol at 30 µmol/l reduced the contraction by 64 ± 3 and 59 ± 1 %, respectively. In detrusor muscles maintained in Ca²⁺-free media and depolarized with 80 mmol/l KCl, the contractile response of muscles to the reintroduction of Ca²⁺ was inhibited in a dose-dependent manner by 17β-estradiol, suggesting that 17β-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/l KC1, 17β-estradiol reduced the myogenic activity with an IC₅₀ of 6.8 ± 1.3 µmol/l. The higher activity of 17β-estradiol in this latter test indicated that estradiol could also possess some K⁺ channel opening activity. Glibenclamide at 1 µmol/l did not affect the relaxant activity of 17β-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, 17β-estradiol possesses K⁺ channel opening activity in guinea pig urinary bladder smooth muscles, activating probably not the adenosine triphosphate sensitive, but the Ca²⁺-dependent large-conductance K⁺ channels.

Steroids and the Endometrium

“…However, the rise in [Ca 2+ ] i reported by Rusko et al [62] was small, despite the high steroid concentration, and it seems doubtful whether an elevation in [Ca 2+ ] i alone accounts for regulation of regional blood flow by oestrogens. As this effect has also been observed in rabbit basilar artery smooth muscle [64] and guinea pig detrusor muscle [65], it may represent a general action of sex steroids on K + channels. As this effect has also been observed in rabbit basilar artery smooth muscle [64] and guinea pig detrusor muscle [65], it may represent a general action of sex steroids on K + channels.…”

Estrogen Modifies an Electrocommunication Signal by Altering the Electrocyte Sodium Current in an Electric Fish,Sternopygus

“…To our knowledge, this is the first report of estrogen influencing sodium current kinetics. Other studies, however, have shown that estrogen modifies sodium current densities in the myometrium (Boyle et al, 1987;Inoue and Sperelakis, 1991) and potassium and /or calcium currents in smooth muscle of the bladder (Yasay et al, 1995), arteries (White et al, 1995), and myometrium (Erulkar et al, 1994;Yamamoto, 1995), and in neurons of the hippocampus (Joels and Karst, 1995), hypothalamus (Lagrange et al, 1995), and neostriatum (Mermelstein et al, 1996). In a case that seems analogous to the opposing actions of estrogen and androgen on electrocytes, Erulkar et al (1994) showed that estrogen and progesterone affect the myometrial potassium channel kinetics in opposite ways: estradiol decreases whereas progesterone increases the time constant of decay of the outward potassium current.…”

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

“…It has been suggested that the transcription factor known as nuclear factor of activated T cells (NFATc3) regulates UBSM contractility predominantly through an NFATc3-dependent increase in BK channel activity (82). In guinea pig UBSM, BK channels can potentially be activated by 17␤-estradiol, leading to UBSM relaxation, but the mechanism of this BK channel modulation by estrogens requires further investigation (158). A recent study revealed that UBSM BK channels are molecular targets for ethanol at physiologically relevant blood alcohol content levels (87).…”