Activation of K+ channels by ritodrine hydrochloride in uterine smooth muscle cells from pregnant women.
This study investigated the mechanism of activation of K+ channels by ritodrine hydrochloride in human myometrial smooth muscle cells. The patch-clamp technique was used for recording single channel currents. Ritodrine (10(-5) M) activated two types of K+ channels in cultured uterine smooth muscle cells from pregnant women: the Ca(2+)-activated K+ (KCa) channel and the ATP-sensitive K+ (KATP) channel. Forskolin (10(-4) M), an activator of adenylate cyclase, and protein kinase A activated the KCa channel. In addition, 10(-4) M GTP activated the KCa channel in inside-out patches using a pipette containing 10(-5) M ritodrine. The KATP channel was activated by protein kinase A, but not by 10(-4) M GTP. The beta-adrenoceptor agonist ritodrine activates two types of K+ channels: the KCa channel via direct gating by GTP-binding proteins and possibly via cAMP-dependent phosphorylation, and the KATP channel possibly via cAMP-dependent phosphorylation. These mechanisms partially explain the relaxing effect of ritodrine hydrochloride.
Hamada
Y
Y
Second Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Nakaya
Y
Y
Hamada
S
S
Kamada
M
M
Aono
T
T
D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects*; D011247:Pregnancy; D012312:Ritodrine / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D015221:Potassium Channels; D005576:Colforsin; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D012312:Ritodrine