Substrate- and inhibitor-specificity of a nonendothelial enzyme which forms [Met 5]-enkephalin from [Met 5]-enkephalin-Arg 6, Phe 7 in isolated rabbit ear artery: Pharmacological characterization

Abstract

The captopril-inhibited enzyme which forms [Met 5]-enkephalin from [Met 5]-enkephalin-Arg 6, Phe 7 in isolated rabbit ear artery was characterized further by using various natural substrate candidates/analogues ([Met 5]-enkephalin-Arg 6, Phe 7 and its amide, [Met 5]-enkephalin, angiotensin I and bradykinin), peptidase inhibitors such as captopril, enalaprilate and thiorphan and by endothel removal. 10 −5 and 10 −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 but did not affect markedly the action of the other peptides. Of the inhibitors, enalaprilate was less effective than captopril, and thiorphan had no effect. The [Met 5]-enkephalin-Arg 6,Phe 7 →[Met 5]-enkephalin conversion was not affected by endothel removal. The substrate and inhibitor spectrum of this non-endothelial enzyme activity bears no relationship in other, hitherto characterized dipeptidylcarboxypeptidases/endopeptidases known to be involved in the metabolism of the tested peptides.