Up-regulation of RGS4 mRNA by opioid receptor agonists in PC12 cells expressing cloned mu- or kappa-opioid receptors.
The regulators of G-protein signaling (RGS) proteins have been shown to modulate the function of some heterotrimeric G-proteins by stimulating the GTPase activity of G-protein alpha subunits. In this study, by northern blotting analysis, we investigated the regulation of RGS4 mRNA by opioid receptor agonists in PC12 cells stably expressing either cloned mu- or kappa-opioid receptors. Treatment with respective opioid receptor agonists (mu: morphine) and [D-Ala(2), MePhe(4), Gly(ol)(5)] enkephalin (DAMGO), kappa: (+)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro-(4,5)dec-8-y1]benzeneacetamide (U69,593)) for 0.5-24 h significantly and transiently increased the expression of RGS4 mRNA by 140-170% of the control level in a concentration-dependent manner which peaked when treated for 2 h, while treatment of non-transfected PC12 cells with opioid receptor agonists did not. The up-regulation of RGS4 mRNA was significantly blocked by co-treatment with respective opioid antagonists (mu: naloxone, kappa: norbinaltorphimine) or pretreatment with pertussis toxin. These results suggest that the activation of mu- or kappa-opioid receptors increases RGS4 mRNA level, which might contribute to opioid desentilization.
Nakagawa
T
T
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Minami
M
M
Satoh
M
M
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D016716:PC12 Cells; D037342:Pertussis Toxin; D020710:RGS Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D020710:RGS Proteins; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C098799:RGS4 protein; D020881:Enkephalin, D-Penicillamine (2,5)-; D037342:Pertussis Toxin