Pharmacological analysis of human D1 AND D2 dopamine receptor missense variants.

Journal of Molecular Neuroscience : MN
Munya A Al-FulaijAlan S Kopin

Abstract

Drugs targeting dopamine receptors have been the focus of much research over the past 30 years, in large part because of their role in treating multiple pathological conditions including Parkinson's disease, schizophrenia, Tourette's syndrome, and hyperprolactinemia. Missense mutations in G protein-coupled receptors (GPCRs) can alter basal and/or ligand-induced signaling, which in turn can affect individuals' susceptibility to disease and/or response to therapeutics. To date, five coding variants in the human D1 receptor (hD1R; T37P, T37R, R50S, S199A, and A229T) and three in the human D2 receptor (hD2R; P310S, S311C, and T351A) have been reported in the NCBI single nucleotide polymorphism database. We utilized site-directed mutagenesis to generate cDNAs encoding these receptor isoforms. After expression in either HEK293 or neuronal GT1 cells, basal and ligand-induced signaling of each of these receptors was determined and compared to wild type. In addition, we investigated expression levels of each recombinant receptor and the effect of inverse agonist administration. Our data demonstrate that naturally occurring amino acid substitutions in the hD1R can lead to alterations in expression levels as well as in basal and ligand-in...Continue Reading

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Citations

Jan 15, 2011·Clinical Reviews in Allergy & Immunology·Michal BenklerYehuda Shoenfeld
Oct 21, 2009·The Journal of Pharmacology and Experimental Therapeutics·Jean-Philippe FortinAlan S Kopin
Sep 14, 2010·The Journal of Pharmacology and Experimental Therapeutics·Carmit GoldsteinAlan S Kopin
May 2, 2012·The Journal of Pharmacology and Experimental Therapeutics·J R DoyleA S Kopin
Nov 18, 2009·The International Journal of Neuroscience·Michal BenklerYehuda Shoenfeld
Oct 30, 2016·The Journal of Pharmacology and Experimental Therapeutics·Bina JulianAlan S Kopin
Dec 21, 2011·The Journal of Interdisciplinary History·Scott Alan Carson
Apr 8, 2020·The Journal of General Physiology·Clara Inés McCarthyJesica Raingo
May 1, 2021·International Journal of Molecular Sciences·Luca MagistrelliFranca Marino

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