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 con traction. Prostaglandins F-2 alpha and E(2) were measured in the buffe r solution. Influx of calcium into uterine smooth muscle cells was ass essed by digital imaging microscopy. RESULTS: After incubation with ur inary trypsin inhibitor or fetal urine, myometrial contractions stimul ated by oxytocin, prostaglandin F-2 alpha or lipopolysaccharide were s uppressed completely. The concentrations of prostaglandins F-2 alpha a nd E(2) in the buffer solution during the isometric contraction test w ere significantly increased by lipopolysaccharide stimulation, but whe n urinary trypsin inhibitor was present in the buffer solution the con centrations of prostaglandins F-2 alpha or E(2) did not change signifi cantly. Preincubation with urinary trypsin inhibitor also inhibited ca lcium influx, resulting in no detectable change in the intracellular f ree calcium concentration of smooth muscle cells. CONCLUSION: We propo sed that urinary trypsin inhibitor from fetal urine inhibits uterine m uscle contraction by regulation of intracellular Ca++.