Butkerait P, Wang H Y, Friedman E
Department of Psychiatry, Medical College of Pennsylvania, Philadelphia.
J Pharmacol Exp Ther. 1994 Oct;271(1):422-8.
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-32P]GTP labeled two striatal proteins with molecular masses of 45 and 40 kD. These proteins were previously identified as alpha subunits of Gs and Gi/Go, respectively. Seven days of reserpine treatment caused a 43% increase in steady-state basal [alpha-32P]GTP binding to striatal G alpha s. Basal [alpha-32P]GTP binding to the 40-kD protein band was unchanged by reserpine treatment. Incubation of membranes with DA stimulated [alpha-32P]GTP binding to both protein bands. Although 10 microM DA stimulated guanine nucleotide binding to G alpha s and G alpha i/o in control tissue by 317% and 236%, respectively, the increases in [alpha-32P]GTP binding in the reserpine-treated animals were 482% (P < .01) and 366% (P < .01), respectively. A single injection of reserpine did not alter basal or DA-stimulated [alpha-32P]GTP binding. Repeated reserpine treatment also enhanced serotonin-induced stimulation of [alpha-32P]GTP binding to striatal G alpha i/o but not to G alpha s. However, carbachol-stimulated binding was unaffected by the treatment Reserpine treatment did not change membrane G alpha s, G alpha i/1/2 or G 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. (ABSTRACT TRUNCATED AT 250 WORDS)
