MK-801 alters RGS2 levels and adenylyl cyclase sensitivity in the rat striatum.
The present report examines the effects of acute NMDA antagonism on Regulator of G Protein Signaling 2 (RGS2) expression and adenylyl cyclase sensitivity in the rat striatum. MK-801 and phencyclidine rapidly down-regulate RGS2 mRNA. The down-regulation of RGS2 by MK-801 was dose dependent and transient. Because previous reports showed that RGS2 attenuates activity of adenylyl cyclase, RGS2 protein level and sensitivity of adenylyl cyclase to forskolin was tested 2 h after administration of MK-801 (1 mg/kg). In striatal membranes of these rats, RGS2 protein level was 17% lower and forskolin-stimulated cAMP production 38% higher than in controls. These findings reveal a cross-talk between NMDA receptors and adenylyl cyclase and suggest a general cross-talk mechanism by which RGS proteins transcriptionally regulated by ionotropic receptors can alter signaling properties of metabotropic receptors.
Taymans
Jean-Marc
JM
Central Nervous System Discovery Research, Psychiatry One Department, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Cruz
Catarina
C
Lesage
Anne
A
Leysen
Josée E
JE
Langlois
Xavier
X
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D020710:RGS Proteins; C087182:RGS2 protein, human; D016291:Dizocilpine Maleate; D000262:Adenylyl Cyclases