Gz proteins are functionally coupled to dopamine D2-like receptors in vivo.
The receptors that couple to the G protein Gz 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 Gz. The dopamine D1-like receptor agonist SKF38393 stimulated comparable locomotor activity in both wildtype mice and mice lacking Galphaz. In contrast, the dopamine D2-like receptor agonist quinpirole suppressed locomotor activity in both groups of mice, but this suppression was significantly smaller in Galphaz 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 Galphaz. In addition, hypothermia and adrenocorticotropic hormone release resulting from activation of dopamine D2-like receptors were also significantly reduced in Galphaz knockout mice. However, adrenocorticotropic hormone secretion induced by corticotrophin releasing hormone and the serotonin 1A receptor agonist 8-hydroxy-dipropylamino-tetralin were similar between wildtype and Galphaz knockout mice. Western blot analysis showed that the expression levels of Galphai, Galphao, Galphas, Galphaq and Gbeta were the same in the brains of mice of both genotypes. Overall, our data suggest that Gz proteins are functionally coupled to dopamine D2-like receptors in vivo.
Leck
Kwong J
KJ
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT Australia, 0200.
Blaha
Charles D
CD
Matthaei
Klaus I
KI
Forster
Gina L
GL
Holgate
Joan
J
Hendry
Ian A
IA
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors
D018491:Dopamine Agonists; D044385:GTP-Binding Protein alpha Subunits; C490964:Gnaz protein, mouse; D017448:Receptors, Dopamine D2; D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine