New perspectives in neuropeptides. Biosynthesis from large precursors. The pro-opio-melanocortin model in the pars intermedia.
Although more and more is known about the nature of neuropeptides, there are two basic questions which need to be looked at in order for the neurophysiologists and the neuropharmacologists to have all the tools necessary for their studies. The first question is the site of biosynthesis of neuropeptides and the second is their biosynthetic pathway. We believe and propose that all neuropeptides will be formed from a larger molecular weight precursor similar to beta-LPH for beta-endorphin. All models of peptide hormones (pro-insulin, pro-PTH, pro-glucagon, beta-lipotropin etc.,) show the same characteristic preferential site of cleavage made of a double basic residue. This is also the type of cleavage recently described by Nakanishi et al. (1979). Using the rat pars intermedia, we showed that this tissue preferentially makes alpha-MSH and beta-endorphin from a large precursor, while beta-LPH and ACTH are short lived intermediates. All products of maturation were identified by chemical analyses leaving no doubt about their nature and identity. We strongly believe that the brain will biosynthesize beta-endorphin and possibly alpha-MSH in similar fashion. We also predict that our results will apply to the other neuropeptides which wil be formed from large precursors. These studies could be very useful in the interpretation of the intricate relationship between neuropeptides and behavioral effects.
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004723:Endorphins / Q000096:biosynthesis; D009074:Melanocyte-Stimulating Hormones / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000096:biosynthesis; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D011333:Pro-Opiomelanocortin; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D001615:beta-Endorphin
D004723:Endorphins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D011498:Protein Precursors; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; C018903:gamma-endorphin, des-Tyr(1)-; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones