The effect of pepstatin A, an inhibitor of the pro-opiomelanocortin (POMC)-converting enzyme, on POMC processing in mouse intermediate pituitary.
In our previous studies, we have purified a unique, paired basic residue-specific, prohormone-converting enzyme from pituitary intermediate lobe secretory vesicles. This enzyme, an aspartyl protease, was shown to cleave the intermediate lobe prohormone, pro-opiomelanocortin (POMC), to adrenocorticotropin, beta-endorphin and a 16 kDa NH2-terminal glycopeptide, in vitro [(1985) J. Biol. Chem. 260, 7194-7205]. To provide some evidence that this enzyme plays a role in prohormone conversion in the intact cell, the ability of pepstatin A, an aspartyl protease inhibitor, to block POMC processing in the mouse intermediate pituitary was investigated. By the use of a radioactive pulse-chase paradigm, [3H]POMC processing was found to be inhibited by 36.4% in pepstatin A-treated intermediate lobes. This result is consistent with the inactivation of pro-opiomelanocortin-converting enzyme by pepstatin A in the intact pituitary and further supports a role of this enzyme in POMC processing in vivo.
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Section on Cellular Neurobiology, National Institute of Child Health and Human Development, Bethesda, MD 20892.
D000818:Animals; D001120:Arginine / Q000378:metabolism; D010450:Endopeptidases; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009842:Oligopeptides / Q000494:pharmacology*; D010436:Pepstatins / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D043484:Proprotein Convertases; D011480:Protease Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012016:Reference Values; D013347:Subcellular Fractions / Q000378:metabolism
D009842:Oligopeptides; D010436:Pepstatins; D011480:Protease Inhibitors; C014195:Streptomyces pepsin inhibitor; D011333:Pro-Opiomelanocortin; D001120:Arginine; D010450:Endopeptidases; D043484:Proprotein Convertases; C031375:pepstatin