New perspectives in signaling mediated by receptors coupled to stimulatory G protein: the emerging significance of cAMP efflux and extracellular cAMP-adenosine pathway

New perspectives in signaling mediated by receptors coupled to stimulatory G protein: the emerging significance of cAMP efflux and extracellular cAMP-adenosine pathway

Author Godinho, Rosely Oliveira Autor UNIFESP Google Scholar
Duarte, Thiago Autor UNIFESP Google Scholar
Pacini, Enio Setsuo Arakaki Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract G protein coupled receptors (GPCRs) linked to stimulatory G (Gs) proteins (GsPCRs) mediate increases in intracellular cyclic AMP as consequence of activation of nine adenylyl cyclases, which differ considerably in their cellular distribution and activation mechanisms. Once produced, cyclic AMP may act via distinct intracellular signaling effectors such as protein kinase A and the exchange proteins activated by cAMP (Epacs). More recently, attention has been focused on the efflux of cAMP through a specific transport system named multidrug resistance proteins that belongs to the ATP-binding cassette transporter superfamily. Outside the cell, cAMP is metabolized into adenosine, which is able to activate four distinct subtypes of adenosine receptors, members of the GPCR family: A(1), A(2)A, A(2B), and A(3). Taking into account that this phenomenon occurs in numerous cell types, as consequence of GsPCR activation and increment in intracellular cAMP levels, in this review, we will discuss the impact of cAMP efflux and the extracellular cAMP-adenosine pathway on the regulation of GsPCR-induced cell response.
Keywords G protein-coupled receptors
cyclic AMP
cAMP efflux
adenosine
adenosine receptors
ABC transporters
ecto-phosphodiesterase
ecto-5'-nucleotidase
Language English
Sponsor Papesp
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number Papesp: 2011/01519-4
Papesp: 2012/20148-0
Date 2015-03-25
Published in Frontiers in Pharmacology. Lausanne: Frontiers Research Foundation, v. 6, 9 p., 2015.
ISSN 1663-9812 (Sherpa/Romeo, impact factor)
Publisher Frontiers Research Foundation
Extent 9
Origin http://dx.doi.org/10.3389/fphar.2015.00058
Access rights Open access Open Access
Type Review
Web of Science ID WOS:000352901500001
URI http://repositorio.unifesp.br/handle/11600/38901

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