Effect of opioid antagonism on beta-endorphin processing and proopiomelanocortin-peptide release in the hypothalamus.
Previous studies have shown that chronic opioid receptor blockade has significant effects on POMC gene expression and peptide levels in the hypothalamus. We have now examined the effects of the opioid antagonist naltrexone on beta-EP processing in the hypothalamus and on the release of 2 POMC-derived peptides, beta-EP and gamma 3-MSH, from the perifused hypothalamus in vitro. The beta-EP immunoactivity in the medial basal hypothalamus (MBH) of 7 rats infused for 1 week with naltrexone by osmotic minipump, was individually analyzed by HPLC and compared to 7 control rats. The mean ratio of beta-EP1-31 compared to beta-EP1-27 plus beta-EP1-26 was 2.34 +/- 0.41 in the naltrexone treated rats, significantly higher than the ratio of 1.26 +/- 0.09 in the control rats (P < 0.02). Thus in the setting of chronic opioid antagonism although beta-EP content decreases, there is relatively more beta-EP1-31, the biologically active opioid form of the peptide, compared to the C-terminally cleaved forms of beta-EP which have reduced biological activity. To study the effects of naltrexone on beta-EP and gamma 3-MSH release, hypothalami were perifused in vitro with 10(-6) M naltrexone. Basal release of gamma 3-MSH was significantly higher from the naltrexone treated brains compared to the controls (221 +/- 20 pg/60 min vs. 161 +/- 6.7 pg/60 min) (P < 0.01); KCl stimulated gamma 3-MSH was also significantly higher in the naltrexone group (951 +/- 94 vs. 543 +/- 85 pg/60 min) (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Jaffe
S B
SB
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Sobieszczyk
S
S
Wardlaw
S L
SL
D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000378:metabolism*
D009292:Narcotic Antagonists; D009271:Naltrexone; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones