pH dependent inhibition of serum oxytocinase activity by prostaglandins and cyclic GMP.
The effect of pH in the range 6.2 to 7.7 on the inhibition of serum oxytocinase (EC 3.4.11.3) activity by various compounds was studied using S-benzyl-L-cysteine-p-nitroanilide (BCN) as substrate. Prostaglandins E1, E2, F2 alpha, 8-bromo-cGMP, cGMP, indomethacin and polyphloretin phosphate (PPP) produced a dose related pH dependent inhibition of serum oxytocinase. Their effect was maximum at pH 6.2 and minimum at pH 7.7. Hypertonic urea and saline also caused pH dependent inhibition; saline being most active at pH 6.2, and urea at pH 7.7. A similar pH dependent inhibition was found when these compounds were examined for their effect on the hydrolysis of L-leucine-p-nitroanilide (LN) by serum aminopeptidases at pH between 6.2 and 7.7. Although the inhibitors were more effective against the hydrolysis of LN than BCN substrate, cGMP and its 8-bromo derivative were more active against the BCN hydrolysis. cAMP, 8-bromo-cAMP, dibutyryl (db)-cAMP, db-cGMP, AMP, ADP, ATP, GDP, GTP, aspirin, sodium salicylate, paracetamol, theophylline and isobutylmethylxanthine (IBMX) at comparable concentrations and within the same pH range had no effect on the hydrolysis of either substrate. It is concluded that in serum obtained during pregnancy, the hydrolysis of LN may largely be attributed to oxytocinase activity. Thus, inhibition of LN hydrolysis by prostaglandins and other substances may be regarded as inhibition of oxytocinase activity.
D000626:Aminopeptidases / Q000097:blood*; D000813:Anilides / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D010122:Cystinyl Aminopeptidase / Q000097:blood*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D011121:Polyphloretin Phosphate / Q000494:pharmacology; D011247:Pregnancy; D011453:Prostaglandins / Q000494:pharmacology*
D000813:Anilides; D011453:Prostaglandins; C016276:8-bromocyclic GMP; C001536:1-leucine-4-nitroanilide; C004559:S-benzyl-L-cysteine-4'-nitroanilide; D011121:Polyphloretin Phosphate; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; D007930:Leucine; D006152:Cyclic GMP; D003545:Cysteine; D007213:Indomethacin