POTASSIUM-CHLORIDE EFFECTS ON THE HORMONAL SIGNAL-TRANSDUCTION MECHANISMS UNDERLYING PHASIC MYOMETRIAL CONTRACTIONS

These studies sought to test the hypothesis that potassium-stimulated phasic myometrial contractions utilize cytosolic calcium oscillation-l ike mechanisms comparable to those activated in response to oxytocin. Uterine tissue was obtained from pro-oestrus/oestrus Sprague-Dawley ra ts. lit vitro isometric contraction studies were performed using longi tudinal myometrial strips; computer digitalized contraction data were analyzed for contraction area, and normalized for tissue cross-section area. Dose-response studies were performed using potassium chloride w ith and without inhibitors of cytosolic calcium oscillation mechanisms . Qualitative inositol-phosphate production studies were performed aft er preloading uterine tissue with [H-3]inositol; subsequently, the ind ividual inositol-phosphates produced in response to stimulation were i solated by anion exchange chromatography. Potassium chloride over a co ncentration of 10 to 30 mM produced a dose-related increase in phasic contractile activity. The potassium-stimulated phasic contractions wer e significantly suppressed in response to inhibition of phospholipase C, stimulation of protein kinase C, inhibition of calcium-induced calc ium release, and prevention of extracellular calcium influx. The quali tative inositol-phosphate production studies confirmed activation of p hospholipase C in response to 20 mM potassium. These studies have prov ided support for the hypothesis that potassium-stimulated phasic myome trial contractions activate intracellular signal transduction mechanis ms comparable to those activated in response to hormonal uterotonic ag onists.