Opioid regulation of proopiomelanocortin (POMC) gene expression in the rat brain as studied by in situ hybridization.
Proopiomelanocortin (POMC) is the precursor of the potent opioid peptide beta-endorphin as well as a number of other active peptides. On the basis of neuroanatomical data indicating the presence of contacts between POMC neurons in the rat arcuate nucleus, it has been proposed that POMC neurons could be autoregulated. In order to investigate the role of opiates in the regulation of POMC gene expression in the rat arcuate nucleus, we studied the effects of chronic administration of the opioid drug morphine and an opiate receptor antagonist naloxone on POMC mRNA levels as measured by in situ hybridization, 4-day treatment with naloxone (4 mg/kg/day) produced a 60% increase in the number of silver grains overlying POMC neurons. Conversely, morphine (40 mg/kg/day) also administered during 4 days decreased the hybridization signal by 30%. The concomitant administration of morphine and naloxone completely prevented the effect of morphine on POMC gene expression indicating that the inhibitory influence of morphine is likely to be mediated by opioid receptors. The data obtained clearly indicate that activation of opioid receptors decreased the biosynthetic activity of POMC neurons and that conversely opiate receptor blockade caused an increase in the activity of these neurons. They are consistent with the hypothesis of an autoregulation of the POMC neuronal system by endogenous opiate peptide(s).
Garcia de Yebenes
E
E
MRC Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
Pelletier
G
G
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D015342:DNA Probes; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D015342:DNA Probes; D012333:RNA, Messenger; D009270:Naloxone; D011333:Pro-Opiomelanocortin; D009020:Morphine