Detailed localization of regulator of G protein signaling 2 messenger ribonucleic acid and protein in the rat brain.
Regulator of G protein signaling (RGS) proteins are a recently identified family of proteins which dampen G protein-coupled receptor-mediated signaling by accelerating the intrinsic GTPase activity of Galpha subunits of heterotrimeric G proteins. More than 20 different RGSs have been identified and at least 10 are expressed in the CNS. The present study describes in detail the localization in the rat brain of one member of this family, RGS2. The distribution of RGS2 mRNA and protein has been studied in parallel by performing in situ hybridization and immunoautoradiography on adjacent rat brain sections. Our localization study reveals that RGS2 mRNA and protein are widely expressed in the brain. Protein and mRNA are mostly colocalized such as in neocortex, piriform cortex, caudate-putamen, septum, hippocampus, locus coeruleus. Some mismatches were also observed such as presence of mRNA but not protein in the paraventricular nucleus, the substantia nigra pars compacta and the red nucleus, suggesting that RGS2 protein is present in neuronal projections. Previous reports describing an induction of RGS2 mRNA in the rat striatum after psychostimulants (amphetamine, cocaine) led us to focus on the distribution of RGS2 in the basal ganglia circuitry. The absence of RGS2 mRNA and protein in the globus pallidus suggests that RGS2 would play its regulatory role more in the direct (striatonigral) than in the indirect (striatopallidal) striatal output pathway. In addition, to delineate the implication of RGS2 in pre- and/or postsynaptic functions in the basal ganglia, we performed lesions of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) and striatal quinolinic acid lesions. The 6-OHDA lesion did not modify RGS2 mRNA or protein levels in the caudate-putamen whereas the intrastriatal quinolinic acid infusion caused a marked reduction of RGS2 mRNA and protein in the lesioned zone. These data indicate that RGS2 is predominantly expressed in intrinsic striatal neurons. Moreover, the absence of detectable change in RGS2 expression after injections of 6-OHDA suggests also that RGS2 is not primarily involved in the hypersensitization of postsynaptic dopamine receptors observed after lesion of the nigrostriatal pathway.
CNS Discovery Research, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
J M
JM
Taymans
C
C
Wintmolders
P
P
Te Riele
M
M
Jurzak
H J
HJ
Groenewegen
J E
JE
Leysen
X
X
Langlois
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D016627:Oxidopamine; D017378:Quinolinic Acid; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics
D018076:DNA, Complementary; D009498:Neurotoxins; D020710:RGS Proteins; D012333:RNA, Messenger; C105345:Rgs2 protein, mouse; D016627:Oxidopamine; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D017378:Quinolinic Acid; D004298:Dopamine