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Interaction of the D-2short dopamine receptor with G proteins: analysis of receptor G protein selectivity

Nickolls, S. A. and Strange, P. G. (2003) Interaction of the D-2short dopamine receptor with G proteins: analysis of receptor G protein selectivity. Biochemical Pharmacology, 65 (7). pp. 1139-1150. ISSN 0006-2952

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To link to this item DOI: 10.1016/s0006-2952(03)00040-6

Abstract/Summary

The human D-2short (D-2S) dopamine receptor has been expressed together with the G proteins Gi2 and Go in insect cells using the baculovirus system. Levels of receptor were determined using [H-3]spiperone binding. Levels of G protein heterotrimer were determined using quantitative Western blot and using [S-35]GTPgammaS saturation binding experiments. Levels of the receptor and G protein and the receptor/G protein ratio were similar in the two preparations. Stimulation of [S-35]GTPgammaS binding by a range of agonists occurred with higher relative efficacy and in some cases higher potency in the preparation expressing Go, indicating that interaction of the D-2S receptor is more efficient with this G protein. The effects of various G protein-selective agents on 10,11-dihydroxy-N-n-propylnorapomorphine ([H-3]NPA) binding were used to examine the receptor/G protein complex in the two preparations. Suramin inhibited [H-3]NPA binding with slightly higher potency in the Gi2 preparation, whereas GppNHp inhibited [H-3]NPA binding with greater potency (similar to6-fold) in the Go preparation. This may imply that the G protein is more readily activated in the D-2S/Go preparation. [H-3]Spiperone binding occurred with an increased B-max in the presence of suramin in the Go preparation but not in the Gi2 preparation, suggesting a higher affinity interaction between the free receptor and this G protein. It is concluded that the higher efficiency activation of Go by the D-2S receptor may be a function of higher affinity receptor/G protein interaction as well as a greater ability to activate the G protein. (C) 2003 Elsevier Science Inc. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences
ID Code:10828
Uncontrolled Keywords:D-2 dopamine receptor, G proteins, selectivity, agonist binding, [S-35]GTP gamma S binding, TERNARY COMPLEX MODEL, ANTERIOR-PITUITARY GLAND, BETA-ADRENERGIC-RECEPTOR, INFECTED INSECT CELLS, D-4.4 RECEPTORS, EFFICACY, ISOFORMS, INHIBITION, EXPRESSION, SURAMIN

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