Gz proteins are functionally coupled to dopamine D2-like receptors in vivo

The receptors that couple to the G protein G(z) in vivo are still relatively unknown. In this study, we investigated the effects of various dopamine receptor agonists in a mouse deficient in the alpha subunit of G(z). The dopamine D1-like receptor agonist SKF38393 stimulated comparable locomotor activity in both wildtype mice and mice lacking G alpha(z). In contrast, the dopamine D2-like receptor agonist quinpirole suppressed locomotor activity in both groups of mice, but this suppression was significantly smaller in G alpha(z) knockout mice. Consistent with these behavioural observations, quinpirole inhibition of dopamine release in the forebrain nucleus accumbens evoked by electrical stimulation of dopamine axons was significantly attenuated in mice lacking G alpha(z). In addition, hypothermia and adrenocorticotropic hormone release resulting from activation of dopamine D2-like receptors were also significantly reduced in G alpha(z) knockout mice. However, adrenocorticotropic hormone secretion induced by corticotrophin releasing hormone and the serotonin 1A receptor agonist 8-hydroxy-dipropylamino-tetralin were similar between wildlype and G alpha(z) knockout mice. Western blot analysis showed that the expression levels of G alpha(i), G alpha(o), G alpha(s), G alpha(q) and G beta were the same in the brains of mice of both genotypes. Overall, our data suggest that G(z) proteins are functionally coupled to dopamine D2-like receptors in vivo. (c) 2006 Elsevier Ltd. All rights reserved.