Multimolecular forms of oxytocinase activity in the human uterus and their inhibition by prostaglandins and cyclic GMP.
Oxytocinase (EC 3.4.11.3) activity was measured in uterine homogenates from pregnant and non-pregnant women using S-benzyl-L-cysteine-p-nitroanilide (BCN) and L-leucine-p-nitroanilide (LN) separately as substrates. There was no significant difference between the specific activity of the enzyme in the pregnant and non-pregnant uterus. The uterine homogenates were also subjected to gel filtration on Ultrogel AcA 22 column and two hydrolyzing activity peaks from the pregnant uterus (PUI, PUII) and three from the non-pregnant uterus (UI, UII, UIII) were obtained. Although the pattern of hydrolysis of the two substrates by the enzyme peaks was similar, the hydrolysis of LN was greater than that of BCN. PUII, UII and UIII showed higher affinity for the substrates than PUI and UI, and the affinity of all isoenzymes was significantly greater for LN than BCN. These uterine oxytocinases appeared to be metallo-aminopeptidases and were potently inhibited by Cu2+, Zn2+ and prostaglandins (PGs). Cyclic GMP (cGMP) and its 8-bromo derivative, however, inhibited only PUI and UI. The divalent cations and PGs were equipotent against the hydrolysis of both substrates, but cGMPs were more effective against BCN hydrolysis. All of these inhibitions depended on the pH of the incubation medium and types of the inhibition by PGs and cGMPs were mixed and uncompetitive respectively. The implications of these findings in relation to human parturition have been discussed.
Roy
A C
AC
Yeang
M
M
Ho
L M
LM
Kottegoda
S R
SR
Ratnam
S S
SS
D000626:Aminopeptidases / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology*; D010122:Cystinyl Aminopeptidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008970:Molecular Weight; D011247:Pregnancy; D011453:Prostaglandins / Q000494:pharmacology*; D014599:Uterus / Q000201:enzymology*
D002413:Cations, Divalent; D011453:Prostaglandins; D004492:Edetic Acid; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; D006152:Cyclic GMP