The posttranslational processing of beta-endorphin in human hypothalamus.
beta-Endorphin is posttranslationally processed to six derivatives, which, although structurally similar, produce distinctly different biological effects. beta-Endorphin 1-31 is a potent opioid receptor agonist, but beta-endorphin 1-27 exhibits antagonist properties, and beta-endorphin 1-26 and the alpha-N-acetyl derivatives of all three peptides lack opioid receptor activity. In the present study, we identified the beta-endorphin peptides synthesized in human hypothalamus using cation exchange HPLC. First, we tested whether postmortem changes occur by storing rat hypothalami at 4 degrees C. This demonstrated that relative amounts of the six beta-endorphin forms did not change for up to 24 h, although total beta-endorphin immunoreactivity significantly declined after 6 h. HPLC analysis of human hypothalami revealed that beta-endorphin 1-31 was the principal form, constituting 58.4 +/- 5.4% of total immunoreactivity. Substantial amounts of beta-endorphin 1-27 (13.4 +/- 1.2%) and beta-endorphin 1-26 (13.1 +/- 1.6%) were also present, but alpha-N-acetylated forms were quantitatively minor, each comprising approximately 5% of total beta-endorphin. A similar processing pattern occurred in preoptic and suprachiasmatic areas of the hypothalamus. These results show that, despite differences in primary sequence, beta-endorphin is processed similarly in both rat and human hypothalamus. Opiate-active beta-endorphin 1-31 is the principal form in both species.
Millington
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WR
Division of Molecular Biology and Biochemistry, University of Missouri, Kansas City 64108-2792.
Smith
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DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001344:Autopsy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis / Q000378:metabolism; D014176:Protein Biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000032:analysis / Q000378:metabolism*
D010455:Peptides; D001615:beta-Endorphin