Pharmacological Characterization of the Receptor Mediating the Anorexigenic Action of the Octadecaneuropeptide: Evidence for an Endozepinergic Tone Regulating Food Intake

作者: Jean-Claude do Rego , Marie-Hélène Orta , Jérôme Leprince , Marie-Christine Tonon , Hubert Vaudry

DOI: 10.1038/SJ.NPP.1301280

关键词:

摘要: Peptides of the endozepine family, including diazepam-binding inhibitor, triakontatetraneuropeptide, and octadecaneuropeptide (ODN), act through three types receptors, that is, central-type benzodiazepine receptors (CBR), peripheral-type (mitochondrial) (PBR) a metabotropic receptor positively coupled to phospholipase C via pertussis toxin-sensitive G protein. We have previously reported ODN exerts potent anorexigenic effect in rat we found action is not affected by mixed CBR/PBR agonist diazepam. In present report, tested possible involvement activity ODN. Intracerebroventricular administration C-terminal octapeptide (OP) its head-to-tail cyclic analog cyclo(1-8)OP (cOP) at dose 100 ng mimicked inhibitory on food intake food-deprived mice. The specific CBR antagonist flumazenil PBR PK11195 did prevent ODN, OP, cOP consumption. contrast, selective cyclo(1-8)[DLeu(5)]OP (100-1000 ng; cDLOP) suppressed cOP. At highest concentration (1000 ng), cDLOP provoked itself significant increase intake. Taken together, results indicate OP mediated activation recently characterized astrocytes. data also suggest endogenous acting this receptor, an tone feeding behavior.

参考文章(33)
Eric A. Barnard, Erminio Costa, Allosteric modulation of amino acid receptors : therapeutic implications Raven Press. ,(1989)
G. Le Fur, M.L. Perrier, N. Vaucher, F. Imbault, A. Flamier, J. Benavides, A. Uzan, C. Renault, M.C. Dubroeucq, C. Guérémy, Peripheral benzodiazepine binding sites: Effect of PK 11195, 1-(2-chlorophenyl)-n-methyl-n-(1-methylpropyl)-3-isoquinolinecarboxamide: I. In vitro studies Life Sciences. ,vol. 32, pp. 1839- 1847 ,(1983) , 10.1016/0024-3205(83)90062-0
Abba J. Kastin, Handbook of biologically active peptides Elsevier, Academic Press. ,(2006)
Jérôme Leprince, Hassan Oulyadi, David Vaudry, Olfa Masmoudi, Pierrick Gandolfo, Christine Patte, Jean Costentin, Jean-Luc Fauchère, Daniel Davoust, Hubert Vaudry, Marie-Christine Tonon, Synthesis, conformational analysis and biological activity of cyclic analogs of the octadecaneuropeptide ODN. Design of a potent endozepine antagonist. FEBS Journal. ,vol. 268, pp. 6045- 6057 ,(2001) , 10.1046/J.0014-2956.2001.02533.X
H. Alho, R. T. Fremeau, H. Tiedge, J. Wilcox, P. Bovolin, J. Brosius, J. L. Roberts, E. Costa, Diazepam binding inhibitor gene expression: location in brain and peripheral tissues of rat Proceedings of the National Academy of Sciences of the United States of America. ,vol. 85, pp. 7018- 7022 ,(1988) , 10.1073/PNAS.85.18.7018
Pierrick Gandolfo, Christine Patte, Jérôme Leprince, Jean-Louis Thoumas, Hubert Vaudry, Marie-Christine Tonon, The stimulatory effect of the octadecaneuropeptide (ODN) on cytosolic Ca2+ in rat astrocytes is not mediated through classical benzodiazepine receptors. European Journal of Pharmacology. ,vol. 322, pp. 275- 281 ,(1997) , 10.1016/S0014-2999(97)00012-5
Pierrick Gandolfo, Estelle Louiset, Christine Patte, J�r�me Leprince, Olfa Masmoudi, Maria Malagon, Francisco Gracia-Navarro, Hubert Vaudry, Marie-Christine Tonon, The triakontatetraneuropeptide TTN increases [Ca2+]i in rat astrocytes through activation of peripheral‐type benzodiazepine receptors Glia. ,vol. 35, pp. 90- 100 ,(2001) , 10.1002/GLIA.1074
Jérôme Leprince, Pierrick Gandolfo, Jean-Louis Thoumas, Christine Patte, Jean-Luc Fauchère, Hubert Vaudry, Marie-Christine Tonon, Structure−Activity Relationships of a Series of Analogues of the Octadecaneuropeptide ODN on Calcium Mobilization in Rat Astrocytes§ Journal of Medicinal Chemistry. ,vol. 41, pp. 4433- 4438 ,(1998) , 10.1021/JM980275D
Erico P. Bonetti, Lorenzo Pieri, Rudolf Cumin, Rudolf Schaffner, Margherita Pieri, Elkan R. Gamzu, Rita K. M. M�ller, Willy Haefely, Benzodiazepine antagonist Ro 15-1788: Neurological and behavioral effects Psychopharmacology. ,vol. 78, pp. 8- 18 ,(1982) , 10.1007/BF00470579