Metalloendopeptidases EC 3.4.24.15 and EC 3.4.24.16: potential roles in vascular physiology

The zinc metalloendopeptidases EC 3.4.24.15 (EP24.15) and EC 3.4.24.16 (EP 24.16) are closely relatedubiquitous enzymes, which have well-defined in vitroactivities in generation and degradation of a range ofspecific peptide targets. Despite this, little is knownregarding their roles in whole animal physiology. One of thepeptides degraded by these enzymes in vitro isbradykinin, a mediator with potent effects on the vasculatureat both systemic and local levels. This review summarises thework that has examined the role of EP 24.15/24.16 inregulation of the vascular effects of bradykinin invivo. This work was made possible by the development of aspecific stable inhibitor of these enzymes, JA-2. Use of thisinhibitor has shown that EP 24.15/24.16 are capable ofregulating responses induced by exogenous bradykinin. Thiseffect was observed at a systemic level with an increase inthe hypotensive effect of intravenous bradykinin. Further workis required to determine whether these enzymes also regulatebradykinin produced endogenously.