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The Triakontatetraneuropeptide (TTN) Stimulates Thymidine Incorporation in Rat Astrocytes Through Peripheral‐Type Benzodiazepine Receptors
Author(s) -
Gandolfo Pierrick,
Patte Christine,
Leprince Jérôme,
Régo JeanLuc Do,
MensahNyagan Ayikoe Guy,
Vaudry Hubert,
To MarieChristine
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750701.x
Subject(s) - autocrine signalling , paracrine signalling , thymidine , receptor , astrocyte , medicine , gabaa receptor , agonist , endocrinology , antagonist , chemistry , biology , microbiology and biotechnology , pharmacology , biochemistry , in vitro , central nervous system
Astrocytes and astrocytoma cells actively express the diazepam‐binding inhibitor (DBI) gene, suggesting that DBI‐processing products may regulate glial cell activity. In the present study, we have investigated the possible effect of one of the DBI‐derived peptides, the triakontatetraneuropeptide (TTN), on [ 3 H]thymidine incorporation in cultured rat astrocytes. Reversed‐phase HPLC analysis of incubation media indicated that TTN is the major form of DBI‐derived peptides released by cultured astrocytes. At very low concentrations (10 ‐14 ‐10 ‐11 M ), TTN induced a dose‐dependent increase in [ 3 H]thymidine incorporation, whereas at higher concentrations (10 ‐10 ‐10 ‐5 M ) the effect of TTN gradually declined. In the same range of concentrations, the specific peripheral‐type benzodiazepine receptor (PBR) agonist Ro 5‐4864 mimicked the bell‐shaped stimulatory effect of TTN on [ 3 H]thymidine incorporation. The PBR antagonist PK11195 (10 ‐6 M ) suppressed the stimulatory action of both TTN and Ro 5‐4864 on [ 3 H]thymidine incorporation, whereas the central‐type benzodiazepine receptor antagonist flumazenil (10 ‐6 M ) had no effect. The present study demonstrates that the endozepine TTN stimulates DNA synthesis in rat glial cells through activation of PBRs. These data strongly suggest that TTN exerts an autocrine/paracrine stimulatory effect on glial cell proliferation.