URINARY TRYPSIN-INHIBITOR PREVENTS UTERINE MUSCLE-CONTRACTION BY INHIBITION OF CA++ INFLUX

OBJECTIVE: The aim of this research was to elucidate the mechanism of action of urinary trypsin inhibitor, a Kunitz-type protease inhibitor, in suppressing uterine muscle contraction. STUDY DESIGN: An isometric uterine contraction test was used to study this inhibitory effect of urinary trypsin inhibitor on the myometrium. Oxytocin, prostaglandin F-2 alpha, and lipopolysaccharide were used to stimulate myometrial contraction. Prostaglandins F-2 alpha and E(2) were measured in the buffer solution. Influx of calcium into uterine smooth muscle cells was assessed by digital imaging microscopy. RESULTS: After incubation with urinary trypsin inhibitor or fetal urine, myometrial contractions stimulated by oxytocin, prostaglandin F-2 alpha or lipopolysaccharide were suppressed completely. The concentrations of prostaglandins F-2 alpha and E(2) in the buffer solution during the isometric contraction test were significantly increased by lipopolysaccharide stimulation, but when urinary trypsin inhibitor was present in the buffer solution the concentrations of prostaglandins F-2 alpha or E(2) did not change significantly. Preincubation with urinary trypsin inhibitor also inhibited calcium influx, resulting in no detectable change in the intracellular free calcium concentration of smooth muscle cells. CONCLUSION: We proposed that urinary trypsin inhibitor from fetal urine inhibits uterine muscle contraction by regulation of intracellular Ca++.