Open AccessSelective Modulation of Gq/Gs pathways by Naphtho Pyrano Pyrimidines As Antagonists of the Neuropeptide S Receptor
Author(s) -
Joshua G. McCoy,
Juan Marugán,
Ke Liu,
Wei Zheng,
Noel Southall,
Wenwei Huang,
Markus Heilig,
Christopher P. Austin
Publication year - 2010
Publication title -
acs chemical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.158
H-Index - 69
ISSN - 1948-7193
DOI - 10.1021/cn100040h
Subject(s) - g protein coupled receptor , receptor , neuropeptide , antagonism , functional selectivity , signal transduction , pharmacology , neuroscience , g protein , biology , chemistry , microbiology and biotechnology , biochemistry
Antagonists of the Neuropeptide S Receptor have been postulated as promising therapeutics in the treatment of respiratory, sleep, anxiety, and addictive disorders. Here we present the SAR of a new series of orthosteric antagonists. Neuropeptide S Receptor signaling is coupled to both Gq and Gs proteins, and we observe that different analogues in this structural series can selectively antagonize these two pathways. Many G-protein coupled receptors transduce signals through multiple pathways. Selective antagonism of these pathways may lead the way to the development of more targeted pharmacological profiles and therapies.