beta-Carboline and diazepam effect on the degradation of enkephalin by the human blood aminopeptidase.
An enkephalin-degrading aminopeptidase (alpha-amino-acyl-peptide hydrolase, EC 3.4.11.11) has been purified from human plasma and has been shown to be the principle responsible for the transient half-life of enkephalin in blood. An inhibitory effect of beta-carbolines and of 3,4-dihydro-beta-carbolines on this enzyme 'in vitro' is reported. The best inhibitor is the 3-carboxylic acid (Ki congruent to 10(-4) M), while the ester, amide, and/or peptide derivatives are less potent. Since some beta-carboline derivatives have recently been shown to possess high affinity for benzodiazepine receptors in brain, the action of diazepam on the aminopeptidase activity was tested and a relevant inhibition of the human enzyme could be demonstrated.
D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000097:blood; D002243:Carbolines / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004743:Enkephalin, Leucine; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D013329:Structure-Activity Relationship
D002243:Carbolines; D007211:Indoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D004743:Enkephalin, Leucine; D000626:Aminopeptidases; C025579:enkephalin degrading enzyme; D003975:Diazepam