title: [35S]GTPgammaS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine.
abstract: Aim of the present study was to investigate possible differences between the human dopamine D4 receptor 48 bp polymorphism variants hD4.2, hD.4. and hD4.7 in agonist stimulated [35S]GTPgammaS binding, to investigate dopamine D4 receptor sodium sensitivity and to further characterize norepinephrine and epinephrine agonism at this receptor. G-protein activation at the receptor variants hD4.2, hD4.4 and hD4.7 expressed in CHO-K1 cells, following stimulation by dopamine, norepinephrine and epinephrine, was investigated using the [35S]GTPgammaS assay at experimental conditions of 10 and 100 mM sodium, respectively. Dopamine displayed a 2 fold higher potency of stimulating [35S]GTPgammaS binding at the hD4.2, compared to the hD4.4 and hD4.7 at 10 mM sodium. A significant difference in sodium sensitivity of basal [35S]GTPgammaS binding was found, with the hD4.7 being 1.7 fold more sensitive than the hD4.4 and 2.5 fold more sensitive than the hD4.2. Norepinephrine and epinephrine both produced concentration-dependent increases in [35S]GTPgammaS binding at all three receptor variants, and epinephrine showed only 2 fold less potency than dopamine. The present results are in certain line with previous reports of functional 2-3 fold differences between the dopamine D4 receptor variants. Agonism of norepinephrine and epinephrine at the dopamine D4 receptor may indicate an important way of cross-reactivity among the different monoamine neurotransmitter systems.
authors.affiliation: Department of General Psychiatry I, Sigmund Freud Clinics Graz, Wagner Jauregg Platz 1, 8053 Graz, Austria. christoph.czermak@lsf-graz.at
authors.forename: Christoph
authors.initials: C
authors.lastname: Czermak
authors.forename: Michael
authors.initials: M
authors.lastname: Lehofer
authors.forename: Peter M
authors.initials: PM
authors.lastname: Liebmann
authors.forename: John
authors.initials: J
authors.lastname: Traynor
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002395:Catecholamines / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D013462:Sulfur Radioisotopes
chemical_list: D002395:Catecholamines; D018491:Dopamine Agonists; D013462:Sulfur Radioisotopes; D050638:Receptors, Dopamine D4; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012965:Sodium Chloride; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine