Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum.
In the brain, dopamine and adenosine stimulate cyclic AMP (cAMP) production through D1 and A2a receptors, respectively. Using mutant mice deficient in the olfactory isoform of the stimulatory GTP-binding protein alpha subunit, Galpha(olf), we demonstrate here the obligatory role of this protein in the adenylyl cyclase responses to dopamine and adenosine in the caudate putamen. Responses to dopamine were also dramatically decreased in the nucleus accumbens but remained unaffected in the prefrontal cortex. Moreover, in the caudate putamen of mice heterozygous for the mutation, the amounts of Galpha(olf) were half of the normal levels, and the efficacy of dopamine- and CGS 21680 A(2) agonist-stimulated cAMP production was decreased. Together, these results identify Galpha(olf) as a critical parameter in the responses to dopamine and adenosine in the basal ganglia.
Corvol
J C
JC
INSERM U536, Institut du Fer à Moulin, Paris, France INSERM U114, Collège de France, Paris, France.
Studler
J M
JM
Schonn
J S
JS
Girault
J A
JA
Hervé
D
D
D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002421:Caudate Nucleus / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology; D003433:Crosses, Genetic; D004298:Dopamine / Q000494:pharmacology*; D044385:GTP-Binding Protein alpha Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000502:physiology; D009928:Organ Specificity; D010627:Phenethylamines / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D020239:Receptor Cross-Talk; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014316:Tritium
D001552:Benzazepines; D044385:GTP-Binding Protein alpha Subunits; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; D018047:Receptors, Purinergic P1; C084618:olfactory G protein subunit alpha olf; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000241:Adenosine; D004298:Dopamine