Role of Phosphodiesterase 1 in the Pathophysiology of Diseases and Potential Therapeutic Opportunities

Overview

Journal Pharmacol Ther

Specialty Pharmacology

Date 2021 Apr 25

PMID 33895190

Citations 16

Authors

Arun Samidurai

Lei Xi

Anindita Das

Audra N Iness

Navin G Vigneshwar

Pin-Lan Li

Dinender K Singla

Sakthivel Muniyan

Surinder K Batra

Rakesh C Kukreja

Affiliations

Soon will be listed here.

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) are superfamily of enzymes that regulate the spatial and temporal relationship of second messenger signaling in the cellular system. Among the 11 different families of PDEs, phosphodiesterase 1 (PDE1) sub-family of enzymes hydrolyze both 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) in a mutually competitive manner. The catalytic activity of PDE1 is stimulated by their binding to Ca/calmodulin (CaM), resulting in the integration of Ca and cyclic nucleotide-mediated signaling in various diseases. The PDE1 family includes three subtypes, PDE1A, PDE1B and PDE1C, which differ for their relative affinities for cAMP and cGMP. These isoforms are differentially expressed throughout the body, including the cardiovascular, central nervous system and other organs. Thus, PDE1 enzymes play a critical role in the pathophysiology of diseases through the fundamental regulation of cAMP and cGMP signaling. This comprehensive review provides the current research on PDE1 and its potential utility as a therapeutic target in diseases including the cardiovascular, pulmonary, metabolic, neurocognitive, renal, cancers and possibly others.

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