Randal A. Skidgel, PhD

Professor of Pharmacology and Anesthesiology
Director of Graduate Studies
Center for Lung and Vascular Biology

We are seeking to understand the important roles of membrane carboxypeptidase M in the regulation of peptide hormone activity and receptor signaling leading to high output nitric oxide production in the cardiovascular system. Our studies revealed that carboxypeptidase M on the surface of cytokine-stimulated endothelial cells efficiently converts bradykinin (a B2 receptor agonist) into des-Arg⁹-bradykinin, a B1 agonist, generating a significant and prolonged output of nitric oxide (NO). We are investigating the structure and function of CPM on the plasma membrane and its ability to form a receptor-enzyme signaling complex with the B1 receptor, a GPCR. We are also studying novel signaling pathways by which the activation of the kinin B1 receptor generates a hyperactive iNOS resulting from activation of the heterotrimeric G protein, Gαi, Src kinase and MAP kinases Erk1/2 and p38. We are also investigating the functional consequences of B1 receptor activation and super-high output NO production in the regulation of endothelial barrier function.

406 CMW
1853 W. Polk St.
(312) 996-9179
rskidgel@uic.edu

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