[Uterotonic action of sigetin and its effect on the Mg2+, ATP-dependent transport and stationary metabolism of Ca2+ through the myometrial sarcolemma].
The effect of sigetin (dipotassium salt, meso-3, 4-di-(n-sulfophenyl)- hexane) on the electrical and mechanical activity, Ca2+, Mg2+-ATPase activity and Mg2+, ATP-dependent Ca2+ transport in uterine smooth muscle have been investigated. Sigetin caused depolarization of the cell membrane, leading to Ca2+ dependent spike discharge and development of mechanical response. Sigetin also produced deceleration of the relaxation of carbachol contracture controlled mostly by the sarcolemmal ATP driven Ca2+ pump. The drug produced strong inhibition of Mg2+, ATP-dependent Ca2+ transport in sarcolemmal vesicles as well as the enzyme and transport activity of the solubilized Ca2+, Mg(2+)-ATPase reconstructed in liposomes. Under the experimental conditions close to the physiological (i.e. in the presence of an outwardly directed Ca2+ gradient) Ca2+ pump normally compensates passive release of this cation. Sigetin was found to shift this calcium equilibrium towards a non-compensated slow diffusion of the cation in the extravesicular space. Addition of sigetin to the incubation medium during the existence of the stationary transmembrane Ca2+ equilibrium stimulates transition of the stationary concentration of the cation in vesicles from high to lower level. The results suggest that the excitatory action of sigetin on myometrial smooth muscle may involve not only indirect stimulation of Ca2+ influx via the voltage operated Ca2+ channels but also through the inhibition of the ATP driven Ca2+ pump of the cell membrane.
Shlykov
S G
SG
Slinchenko
N N
NN
Burdyga
F V
FV
Kosterin
S A
SA
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000187:drug effects*; D005260:Female; D008274:Magnesium / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D012508:Sarcolemma / Q000187:drug effects*; D014590:Uterine Contraction / Q000187:drug effects*
D001557:Benzenesulfonates; C001770:sigetin; D000255:Adenosine Triphosphate; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium
Uterotonicheskoe deĭstvie sigetina i ego vliianie na Mg2+, ATP-zavisimyĭ transport i statsionarnyĭ obmen Ca2+ cherez sarkolemmu miometriia.