Journal article
Increases in guanine nucleotide binding to striatal G proteins is associated with dopamine receptor supersensitivity
The Journal of pharmacology and experimental therapeutics, v 271(1), pp 422-428
01 Jan 1994
PMID: 7965743
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The role of the regulatory guanine nucleotide binding proteins (G proteins) in the development of dopamine (DA) receptor supersensitivity was studied in striatal membranes from reserpine treated rats. [ alpha - super(32)P]GTP labeled two striatal proteins with molecular masses of 45 and 40 kD. These proteins were previously identified as alpha subunits of G sub(s) and G sub(i)/G sub(o), respectively. Seven days of reserpine treatment caused a 43% increase in steady-state basal [ alpha - super(32)P]GTP binding to striatal G sub( alpha s). Basal [ alpha - super(32)P]GTP binding to the 40-kD protein band was unchanged by reserpine treatment. Incubation of membranes with DA stimulated [ alpha - super(32)P]GTP binding to both protein bands. A single injection of reserpine did not alter basal or DA-stimulated [ alpha - super(32)P]GTP binding. Repeated reserpine treatment also enhanced serotonin-induced stimulation of [ alpha - super(32)P]GTP binding to striatal G sub( alpha i/o) but not to G sub( alpha s). However, carbachol-stimulated binding was unaffected by the treatment. Reserpine treatment did not change membrane G sub( alpha s), G sub( alpha i1/2) or G sub( alpha o) levels, as assessed by immunoblotting or by toxin-catalyzed ADP ribosylation. These results suggest that increases in both basal and receptor-mediated activations of G proteins are associated with the development of reserpine-induced striatal DA receptor supersensitivity. This mechanism appears to be of particular importance to mediate the supersensitivity of the D sub(1) DA receptor, which develops during repeated treatment with reserpine.
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Details
- Title
- Increases in guanine nucleotide binding to striatal G proteins is associated with dopamine receptor supersensitivity
- Creators
- P ButkeraitHoau-Yan WangE Friedman
- Publication Details
- The Journal of pharmacology and experimental therapeutics, v 271(1), pp 422-428
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:A1994PN49000055
- Scopus ID
- 2-s2.0-0027997917
- Other Identifier
- 991019184176904721
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- Web of Science research areas
- Pharmacology & Pharmacy