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Activation of receptor gene transcription is required to maintain cell sensitization after agonist exposure - Study on neurotensin receptor

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Najimi, Mustapha [UCL] Souaze, F Mendez, M. Hermans, Emmanuel [UCL] Berbar, T Forgez, P

Neurotensin (NT) acts through specific G protein-coupled receptors to induce effects in the central nervous system and periphery. In this study we have shown that in the human neuroblastoma cell Line CHP 212, an NT agonist, JMV 449, induced high affinity neurotensin receptor (NTR) gene activation. I-125-NT binding of cells challenged with JMV 449 rapidly decreased then reappeared and subsequently stabilized at 50% of the control values after 48 h of agonist exposure. These receptors, which reappeared at the cell surface, are as active as those found in control cells as demonstrated by Ca2+ mobilization. Furthermore, the tyrosine hydroxylase (TH) gene, a known NT target gene, remained activated after prolonged NT agonist exposure in this cell line. In the murine neuroblastoma cell line, N1E-115, NT did not stimulate NTR gene activation but induced NTR mRNA destabilization after long term agonist exposure. In this cell line, NT binding dropped to 15% of control values and remained at this value after agonist treatment. The TH expression, which was originally activated upon NT agonist exposure, decreased to control values after prolonged agonist exposure. These observations combined with the data obtained from a complementary study with HT-29 cells (Souaze, F., Rostene, W., and Forgez, P. (1997) J. Biol. Chem. 272, 10087-10094) revealed the crucial role of agonist-induced receptor gene transcription in the maintenance of cell sensitivity. A model for G protein-coupled receptor regulation induced by prolong and intense agonist stimulation is proposed.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 1998
Language Anglais
Journal information "Journal of Biological Chemistry" - Vol. 273, no. 34, p. 21634-21641 (1998)
Peer reviewed yes
Publisher Amer Soc Biochemistry Molecular Biology Inc (Bethesda)
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL - MD/FSIO - Département de physiologie et pharmacologie
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Bibliographic reference Najimi, Mustapha ; Souaze, F ; Mendez, M. ; Hermans, Emmanuel ; Berbar, T ; et. al. Activation of receptor gene transcription is required to maintain cell sensitization after agonist exposure - Study on neurotensin receptor. In: Journal of Biological Chemistry, Vol. 273, no. 34, p. 21634-21641 (1998)
Permanent URL http://hdl.handle.net/2078.1/45123