Faculty Collaboration Database

Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation. Proc Natl Acad Sci U S A 2017 May 30;114(22):5595-5600

Date

05/14/2017

Pubmed ID

28500275

Pubmed Central ID

PMC5465905

DOI

10.1073/pnas.1618422114

Scopus ID

2-s2.0-85020029345 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Recently, an alternative theory concerning the method by which olfactory proteins are activated has garnered attention. This theory proposes that the activation of olfactory G protein-coupled receptors occurs by an inelastic electron tunneling mechanism that is mediated through the presence of an agonist with an appropriate vibrational state to accept the inelastic portion of the tunneling electron's energy. In a recent series of papers, some suggestive theoretical evidence has been offered that this theory may be applied to nonolfactory G protein-coupled receptors (GPCRs), including those associated with the central nervous system (CNS). [Chee HK, June OS (2013) Genomics Inform 11(4):282-288; Chee HK, et al. (2015) FEBS Lett 589(4):548-552; Oh SJ (2012) Genomics Inform 10(2):128-132]. Herein, we test the viability of this idea, both by receptor affinity and receptor activation measured by calcium flux. This test was performed using a pair of well-characterized agonists for members of the 5-HT₂ class of serotonin receptors, 2,5-dimethoxy-4-iodoamphetamine (DOI) and N,N-dimethyllysergamide (DAM-57), and their respective deuterated isotopologues. No evidence was found that selective deuteration affected either the binding affinity or the activation by the selected ligands for the examined members of the 5-HT₂ receptor class.

Author List

Hoehn RD, Nichols DE, McCorvy JD, Neven H, Kais S

Author

John McCorvy PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amphetamines
Enzyme Activation
Heterocyclic Compounds, 4 or More Rings
Humans
Receptor, Serotonin, 5-HT2A
Serotonin 5-HT2 Receptor Agonists
Signal Transduction
Smell
Vibration