GOLF AND GS IN RAT BASAL GANGLIA - POSSIBLE INVOLVEMENT OF GOLF IN THE COUPLING OF DOPAMINE-D1 RECEPTOR WITH ADENYLYL CYCLASE

Using specific antibodies and cDNA probes, we have investigated, in ra t basal ganglia, the distribution and the regulation of the expression of the a subunits of G(s) and G(olf), two GTP-binding proteins (G-pro teins) that stimulate adenylyl cyclase. We confirmed that G(olf)alpha is highly expressed in caudate-putamen, nucleus accumbens, and olfacto ry tubercle, whereas G(s)alpha is less abundant in these areas than in the other brain regions. Intrastriatal injections of quinolinic acid decreased dramatically the levels of G(olf)alpha protein in the striat um and the substantia nigra, and those of G(olf)alpha mRNA in the stri atum. Retrograde lesions of striatonigral neurons with volkensin reduc ed markedly the levels of D1 dopamine (DA) binding sites, as well as t hose of G(olf)alpha protein and mRNA in the striatum, without altering D2 binding sites. In contrast, both types of lesions increased the le vels of G(s)alpha protein in the striatum and substantia nigra. Immuno cytochemistry showed the presence of G(olf)alpha protein in striatal m edium-sized neurons and in several other neuronal populations. These r esults demonstrate that striatonigral neurons contain high levels of G (olf)alpha and little, if any, G(s)alpha, suggesting that the coupling of D1 receptor to adenylyl cyclase is provided by G(olf)alpha. The le vels of G(olf)alpha were five- to sixfold higher in the striatum than in the substantia nigra, indicating a preferential localization of G(o lf)alpha in the somatodendritic region of striatonigral neurons and pr oviding a basis for the low efficiency of D1 receptor coupling in the substantia nigra. Six weeks after 6-hydroxydopamine lesions of DA neur ons, an increase in G(olf)alpha (+53%) and G(s)alpha (+64%) proteins w as observed in the striatum. This increase in G(olf)alpha levels may a ccount for the DA-activated adenylyl cyclase supersensitivity, without change in D1 receptors density, that follows destruction of DA neuron s. Fine regulation of the levels of G(olf)alpha in physiological or pa thological situations may be a critical parameter for the efficiency o f DA neurotransmission.