Evidence for conversion of N-Tyr-MIF-1 into MIF-1 by a specific brain aminopeptidase |
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Authors: | Neville Marks Martin J. Berg Abba J. Kastin David H. Coy |
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Affiliation: | 1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, Ward''s Island, NY 10035, U.S.A.;1. Endocrinology Section, VA Medical Center, New Orleans, LA 70146, U.S.A.;2. Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70146, U.S.A. |
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Abstract: | N-Tyr-MIF-1 (Tyr-Pro-Leu-Gly·NH2), an immunoreactive neuropeptide exhibiting saturable high affinity binding in rat brain was found to be converted into MIF-1 (Pro-Leu-Gly·NH2) by a specific brain aminopeptidase present in rat brain homogenates or cytosol, but with low activity associated with synaptosomal plasma membranes and microsomes. Conversion occurred at a rate of 16 μmol per g w/wt per h and was unaffected by puromycin but inhibited by bestatin (I50, 5 × 10?5 M). Aminopeptidases purified from cytosolic fractions of rat brain (arylamidase), mouse brain (Mn2+-activated aminopeptidase) or porcine kidney (leucine aminopeptidase) were inactive towards N-Tyr-MIF-1 but degraded MIF-1 with release of Leu-Gly·NH2 as detected by RP-HPLC procedures. Morphiceptin (Tyr-Pro-Phe-Pro·NH2), a μ opioid agonist, also acted as a substrate for the N-Tyr-MIF-1 converting enzyme with cleavage of the Tyr-Pro bond. These tetrapeptides, but not MIF-1 or its N-blocked analogs, were degraded in vitro by a metalloendopeptidase purified from kidney membranes. Since dipeptide products were not detected for crude extracts, a significant role for brain metalloendopeptidase on turnover can be excluded. Thus the results point to the presence of a specific (X-Pro-degrading) aminopeptidase in brain cytosol as an enzyme responsible for converting N-Tyr-MIF-1 and inactivating morphiceptin. |
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Keywords: | MIF-1 melanotropin inhibiting factor LAP leucine aminopeptidase PLG prolyl-leucyl-glycinamide |
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