Differential localization of the mRNAs for the pertussis toxin insensitive G-protein alpha sub-units Gq, G11, and Gz in the rat brain, and regulation of their expression after striatal deafferentation

The corticostriatal pathway is among the largest glutamatergic pathways in the brain, and of particular interest to the study of glutamatergic transmission. The metabotropic glutamate receptors (mGluRs) couple the actions of glutamate to intracellular second messenger systems through G-proteins. The most prominent of the mGluRs present in the target of this pathway, the striatum, is mGluR5. The identity of the G-proteins mediating the actions of mGluR5 are unknown, but the receptor is linked to stimulation of phosphoinositide (PI) turnover and largely resistant to the effects of pertussis toxin, which inhibits some G-proteins. We used in situ hybridization to examine the expression and regulation of three pertussis toxin insensitive G-protein alpha sub-units: G(q), G(11), and G(z). We found that these mRNAs are differentially distributed in the rat brain, but all three are expressed by striatal neurons. After glutamatergic deafferentation of the striatum by decortication, there is a modest upregulation of G(11) mRNA, while expression of G(q) and G(z) are unchanged. Following dopaminergic deafferentation, expression of G(q), G(11), and G(z) are not altered, although expression of the pertussis-sensitive sub-unit G(o) is increased. Our data suggests that G(z), G(q), and G(11) are each expressed by striatal neurons, and therefore may be involved in mediating the actions of mGluR5 in these cells. After decortication G(11) is upregulated, but the magnitude of this effect is small, and alone seems insufficient to account for the marked biochemical supersensitivity of glutamate-stimulated PI turnover which is observed. (C) 1998 Elsevier Science B.V.