SUBSTRATE-SPECIFICITY AND INHIBITOR-SPECIFICITY OF A NON-ENDOTHELIAL ENZYME WHICH FORMS [MET(5)]-ENKEPHALIN FROM [MET(5)]-ENKEPHALIN-ARG(6), PHE(7) IN ISOLATED RABBIT EAR ARTERY - PHARMACOLOGICAL CHARACTERIZATION

The captopril-inhibited enzyme which forms [Met(5)]-enkephalin from [M et(5)]-enkephalin-Arg(6),Phe(7) in isolated rabbit ear artery was char acterized further by using various natural substrate candidates/analog ues ([Met(5)]-enkephalin-Arg(6),Phe(7) and its amide, [Met(5)]-enkepha lin, angiotensin I and bradykinin), peptidase inhibitors such as capto pril, enalaprilate and thiorphan and by endothel removal. 10(-5) and 1 0(-4) M but not 10(-6) M captopril reduced the effectiveness of [Met(5 )]-enkephalin-Arg(6),phe(7) and potentiated the effect of bradykinin b ut did not affect markedly the action of the other peptides. Of the in hibitors, enalaprilate was less effective than captopril, and thiorpha n had no effect. The [Met(5)]-enkephalin-Arg(6),Phe(7) --> [Met(5)]-en kephalin conversion was not affected by endothel removal. The substrat e and inhibitor spectrum of this non-endothelial enzyme activity bears no relationship in other, hitherto characterized dipeptidylcarboxypep tidases/endopeptidas known to be involved in the metabolism of the tes ted peptides.