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Regulation of the neurotensin NT 1 receptor in the developing rat brain following chronic treatment with the antagonist SR 48692
Author(s) -
LépéeLorgeoux Isabelle,
Betancur Catalina,
Souazé Frédérique,
Rostène William,
Bérod Anne,
Pélaprat Didier
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000501)60:3<362::aid-jnr11>3.0.co;2-f
Subject(s) - neurotensin , neurotensin receptor , medicine , endocrinology , receptor , agonist , biology , neuropeptide , in situ hybridization , receptor antagonist , antagonist , messenger rna , biochemistry , gene
The aim of the present study was to investigate the role of neurotensin in the regulation of NT 1 receptors during postnatal development in the rat brain. Characterization of the ontogeny of neurotensin concentration and [ 125 I]neurotensin binding to NT 1 receptors in the brain at different embryonic and postnatal stages showed that neurotensin was highly expressed at birth, reaching peak levels at postnatal day 5 (P5) and decreasing thereafter. The transient rise in neurotensin levels preceded the maximal expression of NT 1 receptors, observed at P10, suggesting that neurotensin may influence the developmental profile of NT 1 receptors. Using primary cultures of cerebral cortex neurons from fetal rats, we showed that exposure to the neurotensin agonist JMV 449 (1 nM) decreased (−43%) the amount of NT 1 receptor mRNA measured by reverse transcription‐PCR, an effect that was abolished by the nonpeptide NT 1 receptor antagonist SR 48692 (1 μM). However, daily injection of SR 48692 to rat pups from birth for 5, 9, or 15 days did not modify [ 125 I]neurotensin binding in brain membrane homogenates. Moreover, postnatal blockade of neurotensin transmission did not alter the density and distribution of NT 1 receptors assessed by quantitative autoradiography nor NT 1 receptor mRNA expression measured by in situ hybridization in the cerebral cortex, caudate‐putamen, and midbrain. These results suggest that although NT 1 receptor expression can be regulated in vitro by the agonist at an early developmental stage, neurotensin is not a major factor in the establishment of the ontogenetic pattern of NT receptors in the rat brain. J. Neurosci. Res. 60:362–369, 2000 © 2000 Wiley‐Liss, Inc.