Regulation of proopiomelanocortin messenger RNA concentrations by opioid peptides in primary cell cultures of rat hypothalamus.
The effects of opioid peptides on a 1.1-kb long proopiomelanocortin messenger RNA (POMC mRNA) have been investigated in rat hypothalamic cells maintained in culture. Most opioid peptides exerted an inhibitory control on POMC mRNA steady-state concentrations. beta-Endorphin caused a 65% maximal inhibitory effect (IC50 = 6.1 x 10(-9) M) while slightly less inhibition was caused by Met- and Leu-enkephalin, dynorphin A and DADLE ([D-Ala2,D-Leu5] enkephalin). The effects of beta-endorphin and of Met-enkephalin were completely reversed by the delta opioid antagonist ICI 174,864 while the kappa-receptor specific antagonist binaltorphimine or the sigma-receptor specific antagonist DTG (1,3-di(2-tolyl) guanidine) respectively blocked the inhibitory actions of dynorphin A and of DADLE. The mu-receptor specific agonist DAGO ([D-Ala2,N-Me-Phe4,Gly5-OL]enkephalin) did not affect POMC mRNA levels. The failure of the dopaminergic D2 antagonist haloperidol to modify the inhibitory effects of opioid peptides argues for a direct inhibitory opioid peptide modulation of hypothalamic POMC mRNA levels mediated by the delta-, kappa- and sigma- (but not mu-) receptors in vivo.
l'Héreault
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Molecular Psychogenetics Laboratory, Laval University, Ste Foy, Que., Canada.
Barden
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D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology; D004622:Embryo, Mammalian; D004723:Endorphins / Q000494:pharmacology*; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D015347:RNA Probes; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004723:Endorphins; D015347:RNA Probes; D012333:RNA, Messenger; D016308:Enkephalin, Leucine-2-Alanine; D011333:Pro-Opiomelanocortin; D006220:Haloperidol; D004298:Dopamine