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Interactions between carboxypeptidase M and kinin B1 receptor in endothelial cells

Item Type:Article
Title:Interactions between carboxypeptidase M and kinin B1 receptor in endothelial cells
Creators Name:Guimarães, P.B. and da Silva, R.F. and Hoff, C.C. and Fernandes, L. and Nakaie, C.R. and Chagas, J.R. and Karaoglanovic Carmona, A. and Bader, M. and Pesquero, J.B.
Abstract:INTRODUCTION: Carboxypeptidase M (CPM) is a glycosylphosphatidylinositol anchored enzyme that plays an important role in the kallikrein–kinin system (KKS). CPM catalytic domain hydrolyzes Arg from C-terminal peptides (i.e., bradykinin and kallidin), generating des-Arg-kinins, the agonists of B(1) receptor (B(1)R). It is known that CPM and kinin B(1)R are co-localized in the plasma membrane microdomains, where they interact with each other, facilitating receptor signaling. AIMS: We hypothesized here that this CPM-B(1)R interaction could also affect the activity of the enzyme. METHODS: Thus, in this work, we evaluated the impact of B(1)R presence or absence on CPM activity and expression, using primary culture of microvascular endothelial cells from wild-type, kinin B(1)R knockout mice (B(1)(-/-)), and transgenic rats overexpressing B(1) receptor exclusively in the endothelium. In addition, HEK293T cells, as wells as B(1)(-/-) primary culture of endothelial cells, both transfected with B(1)R, were also used. RESULTS: CPM expression and activity were downregulated in cells of knockout mice compared to control and this reduction was rescued after B(1)R transfection. Cells overexpressing B(1)R presented higher levels of CPM mRNA, protein, and activity. This profile was reverted by pre-incubation with the B(1)R antagonist, R715, in highly expressing receptor cells. CONCLUSIONS: Our data show that kinin B(1)R positively modulates both CPM expression and activity, suggesting that CPM-B(1)R interaction in membrane microdomains might affect enzyme activity, beyond interfering in receptors signaling. This work highlights the interactions among different components of KKS and contributes to a better understanding of its patho-physiological role.
Keywords:Carboxypeptidase M, B(1) Receptor, Kinins, Microdomains, Enzymatic Activity, Animals, Mice, Rats
Source:Inflammation Research
Page Range:845-855
Date:October 2019
Official Publication:https://doi.org/10.1007/s00011-019-01264-6
PubMed:View item in PubMed

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