On the Mechanism of Action of Prolylcarboxypeptidase

Many mechanisms are involved in the regulation of blood pressure. Among the molecules, hormones, and factors known to be involved in blood pressure regulation, PRCP can generate the most potent inflammatory vasodilator molecules, including nitric oxide (Zhao et al., 2001c), prostaglandins (Kolte et al., 2011), bradykinin (BK)-(Chajkowski et al., 2010) and angiotensin 1-7 (Ang1-7)-(Mallela et al., 2008) dependent pathways in the endothelium and astrocytes. Experimental evidence suggest that PRCP appears to metabolize its main substrates, des-Arg9-bradykinin (des-Arg9-BK, BK1-8)(Chajkowski et al., 2010) and alphamelanocyte stimulating hormone 1-13 (-MSH1-13)(Wallingford et al., 2009), to prevent the production of prostaglandins and NO, indicating that the enzyme may promote antiinflammatory effects in cardiovascular and cerebrovascular systems. Evidence shows that Prcp gene expression is elevated in the developing murine brain vasculature during the intermediate phase of chick chorio-allantoic membrane (CAM)(Javerzat et al., 2009), suggesting that PRCP has a role during the active phase of vascular remodeling. Interestingly, Prcp gene is overexpressed in glioblastoma and it is suggested that PRCP also has a role in tumor angiogenesis(Javerzat et al., 2009). Thus, PRCP plays important roles in response to stress and may be an endothelial gate-keeper regulating blood flow, which tightly regulates endothelial barrier function. The historical perspective of knowledge of PRCP and its roles in physiological and cardiovascular diseases such as inflammation, hypertension, thrombosis, and obesity is tabulated in Table 1.