Direct measurement of intracellular free calcium in cultured human puerperal myometrial cells stimulated by oxytocin: effects of extracellular calcium and calcium channel blockers.
The changes in intracellular free calcium concentration ([Ca2+]i) induced by oxytocin in single cells of cultured human puerperal myometrium were measured with the calcium-sensitive fluorescent dye fura 2 in a digital imaging fluorescence microscopic system. Oxytocin at concentrations of 30-300 nmol/L induced a dose-dependent increase in [Ca2+]i with a peak at 20 seconds. This increase depended mainly on extracellular calcium ([Ca2+]ex) at concentrations of 0.6-4.8 mmol/L. In the absence of [Ca2+]ex, the increase was only 16% of that in its presence. The voltage-sensitive calcium channel blockers nicardipine, nifedipine, and nitrendipine had similar effects, causing significant suppression of the increase in [Ca2+]i induced by oxytocin. Diltiazem also suppressed the increase in [Ca2+]i, though less than the other calcium channel blockers. These data indicate that the increase in [Ca2+]i induced by oxytocin is predominantly dependent upon [Ca2+]ex. Furthermore, the data explain why calcium channel blockers are effective for weakening uterine muscle contractions and indicate which type of blocker is most effective.
Tasaka
K
K
Department of Gynecology, Center for Adult Diseases, Osaka, Japan.
Masumoto
N
N
Miyake
A
A
Tanizawa
O
O
D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008856:Microscopy, Fluorescence; D009215:Myometrium / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology*; D049590:Postpartum Period / Q000378:metabolism
D002121:Calcium Channel Blockers; D010121:Oxytocin; D009568:Nitrendipine; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium