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.


METHODS
An isometric uterine contraction test was used to study this inhibitory effect of urinary trypsin inhibitor on the myometrium. Oxytocin, prostaglandin F2 alpha, and lipopolysaccharide were used to stimulate myometrial contraction. Prostaglandins F2 alpha and E2 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 F2 alpha or lipopolysaccharide were suppressed completely. The concentrations of prostaglandins F2 alpha and E2 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 F2 alpha or E2 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.


CONCLUSIONS
We proposed that urinary trypsin inhibitor from fetal urine inhibits uterine muscle contraction by regulation of intracellular Ca++.
Kanayama
N
N
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Japan.
el Maradny
E
E
Halim
A
A
Liping
S
S
Maehara
K
K
Kajiwara
Y
Y
Terao
T
T
D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D013268:Stimulation, Chemical; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D006023:Glycoproteins; D008070:Lipopolysaccharides; D014361:Trypsin Inhibitors; D010121:Oxytocin; D015237:Dinoprost; C028665:urinastatin; D002118:Calcium