Opposite modulation of regulators of G protein signalling-2 RGS2 and RGS4 expression by dopamine receptors in the rat striatum.
The role of dopaminergic transmission on striatal mRNA levels of regulators of G protein signalling proteins RGS 2-12 was evaluated by quantitative in situ hybridisation. A single injection of L-dopa (50 mg/kg i.p.) significantly increased the RGS2 mRNA level (by 25%), an effect that was specifically abolished by the D1 dopamine receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (R(+)-SCH23390), but not changed by S(-)-eticlopride. Interestingly, the administration of this D2 dopamine receptor antagonist alone markedly enhanced the expression of RGS2 (by 71%), which suggests a constitutive inhibition of RGS2 expression by D2 dopamine receptors. Opposite results were obtained concerning the regulation of RGS4 since L-dopa alone was without effect whereas co-administration of L-dopa and R(+)-SCH23390 significantly enhanced the RGS4 mRNA levels (by 38%). In conclusion, D1 and D2 dopamine receptors appear to mediate opposite regulatory effects on RGS2 and RGS4 expression in the striatum.
Geurts
Muriel
M
Laboratoire de Pharmacologie Expérimentale (FARL), Université catholique de Louvain, 54 10, Avenue Hippocrate 54, B-1200, Brussels, Belgium.
Hermans
Emmanuel
E
Maloteaux
Jean Marie
JM
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D017403:In Situ Hybridization; D007980:Levodopa / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000187:drug effects; D020710:RGS Proteins / Q000096:biosynthesis* / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012457:Salicylamides / Q000037:antagonists & inhibitors
D001552:Benzazepines; D018492:Dopamine Antagonists; D016760:Proto-Oncogene Proteins c-fos; D020710:RGS Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D007980:Levodopa; C045989:eticlopride; C035420:levodopa methyl ester