G protein-coupled receptor signaling in cardiac nuclear membranes.

Abstract:

:G protein-coupled receptors (GPCRs) play key physiological roles and represent a significant target for drug development. However, historically, drugs were developed with the understanding that GPCRs as a therapeutic target exist solely on cell surface membranes. More recently, GPCRs have been detected on intracellular membranes, including the nuclear membrane, and the concept that intracellular GPCRs are functional is become more widely accepted. Nuclear GPCRs couple to effectors and regulate signaling pathways, analogous to their counterparts at the cell surface, but may serve distinct biological roles. Hence, the physiological responses mediated by GPCR ligands, or pharmacological agents, result from the integration of their actions at extracellular and intracellular receptors. The net effect depends on the ability of a given ligand or drug to access intracellular receptors, as dictated by its structure, lipophilic properties, and affinity for nuclear receptors. This review will discuss angiotensin II, endothelin, and β-adrenergic receptors located on the nuclear envelope in cardiac cells in terms of their origin, activation, and role in cardiovascular function and pathology.

journal_name

J Cardiovasc Pharmacol

authors

Branco AF,Allen BG

doi

10.1097/FJC.0000000000000196

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

101-9

issue

2

eissn

0160-2446

issn

1533-4023

pii

00005344-201502000-00003

journal_volume

65

pub_type

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