title: Involvement of metallo-endopeptidase in degradation of luteinizing hormone-releasing hormone by neuronal and glial cells cultured from rat fetal brain.
abstract: Luteinizing hormone-releasing hormone (LHRH) was degraded by neuronal and glial cells cultured from fetal rat brain. The degradation of LHRH by neuronal cells was strongly inhibited by a metal chelator. Captopril only inhibited by generation of fragment (1-3) from fragment (1-5). In the presence of captopril, fragment (1-5) accumulated in the highest amount among the N-terminal fragments identified. The initial cleavage of LHRH, as determined by following the loss of the LHRH peak, was strongly inhibited by thiol-blocking reagents, as well as metal chelators. The results with glial cells were almost the same as those seen with neuronal cells. Thus, we propose that a thiol-dependent membrane-bound metallo-endopeptidase plays a major role in the initial stage of degradation of LHRH at the Tyr5-Gly6 bond in both neurons and glia. Angiotensin-converting enzyme is involved in the secondary process of the LHRH degradation in both cells.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo Japan.
authors.forename: C
authors.initials: C
authors.lastname: Sakurada
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Yokosawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D005333:Fetus; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010446:Peptide Fragments / Q000302:isolation & purification; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats
chemical_list: D010446:Peptide Fragments; D011480:Protease Inhibitors; D007987:Gonadotropin-Releasing Hormone; D002216:Captopril; D008666:Metalloendopeptidases