Altstein, M., Department of Neurobiology The Weizmann Institute of Science Rehovot, Israel
Mittman, S., Department of Neurobiology The Weizmann Institute of Science Rehovot, Israel
Vogel, Z., Department of Neurobiology The Weizmann Institute of Science Rehovot, Israel

Several barbiturates inhibit the degradation of enkephalin by the enzyme enkephalinase, a membrane-associated endopeptidase of rat striatum. The barbiturates vary largely in their inhibitory potential toward this enzymatic activity. Secobarbital, pentobarbital, phenobarbital and barbital inhibit the hydrolysis of Leu-enkephalin with IC50 of 8 × 10-6M, 1.8 × 10-5M, 7 × 10-5M and 4 × 10-4M, respectively. The N-1 methyl substituted barbiturates, methohexital and hexobarbital, as well as barbituric acid have very low or no inhibitory activity. The inhibition of Leu-enkephalin degradation by secobarbital exhibits mixed noncompetitive-competitive kinetics with KI S of 2 × 10-5M and KI I of 6 × 10-5M. Solubilization of enkephalinase from the membranes with Triton X-100 does not effect the inhibition by the barbiturates. The barbiturates do not inhibit two other brain enzymes shown to degrade enkephalin, i.e. the enkephalin-degrading aminopeptidase and enkephalinase B. In addition, the hydrolysis of enkephalin by carboxypeptidase A or by thermolysin is not affected by the barbiturates. © 1981.