G(olf) and Gs in rat basal ganglia: possible involvement of G(olf) in the coupling of dopamine D1 receptor with adenylyl cyclase

Abstract

Using specific antibodies and cDNA probes, we have investigated, in rat basal ganglia, the distribution and the regulation of the expression of the alpha subunits of Gs and G(olf), two GTP-binding proteins (G-proteins) that stimulate adenylyl cyclase. We confirmed that G(olf) alpha is highly expressed in caudate-putamen, nucleus accumbens, and olfactory tubercle, whereas Gs 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 striatum and the substantia nigra, and those of G(olf) alpha mRNA in the striatum. Retrograde lesions of striatonigral neurons with volkensin reduced markedly the levels of D1 dopamine (DA) binding sites, as well as those of G(olf) alpha protein and mRNA in the striatum, without altering D2 binding sites. In contrast, both types of lesions increased the levels of Gs alpha protein in the striatum and substantia nigra. Immunocytochemistry showed the presence of G(olf) alpha protein in striatal medium-sized neurons and in several other neuronal populations. These results demonstrate that striatonigral neurons contain high levels of G(olf) alpha and little, if any, Gs alpha, suggesting that the coupling of D1 receptor to adenylyl cyclase is provided by G(olf) alpha. The levels of G(olf) alpha were five- to sixfold higher in the striatum than in the substantia nigra, indicating a preferential localization of G(olf) alpha in the somatodendritic region of striatonigral neurons and providing a basis for the low efficiency of D1 receptor coupling in the substantia nigra. Six weeks after 6-hydroxydopamine lesions of DA neurons, an increase in G(olf) alpha (+53%) and Gs alpha (+64%) proteins was observed in the striatum. This increase in G(olf) alpha levels may account for the DA-activated adenylyl cyclase supersensitivity, without change in D1 receptors density, that follows destruction of DA neurons. Fine regulation of the levels of G(olf) alpha in physiological or pathological situations may be a critical parameter for the efficiency of DA neurotransmission.

Metabotropic mGlu5 receptors regulate adenosine A 2A receptor signaling

“…The results obtained in this study suggest that functional coupling of mGlu5 receptors is likely to be different in the two types of medium spiny neurons. As a result, the availability of Golf␣, which couples dopamine D1-type receptors and adenosine A 2A receptors to adenylyl cyclase in neostriatum (21,22), may be different in the two types of medium spiny neuron. Alternatively, the actions of mGlu5 receptors may be regulated in different ways by other G protein-coupled receptors, such as dopamine D2-type receptors and opioid receptors, within the two types of medium-sized spiny neurons (23,24).…”

Functional expression of the olfactory signaling system in the kidney

“…1C, we detect the 55-kDa AC3 band in both mouse and rat kidneys along with the additional 90-kDa band. G olf is typically detected as a band of 43-46 kDa, and an additional band at 77 kDa has been reported (6,12). As shown in Fig.…”

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

“…Although Gaolf is very abundant in the striatum, it is not expressed in other regions such as the prefrontal cortex (Herve et al, 1993) where D1R are coupled to Gas . Functional effects of repeated administration of psychostimulants on cortico-striatal neurons may be essential for sensitized and conditioned responses to psychostimulants but are unlikely to be changed by reduced Gaolf levels.…”