Abstract：
:In order to better understand the neuroleptic-like effects of neurotensin in vivo, the effects of neurotensin in vitro on dopamine D2 and D1 agonist and antagonist binding sites were characterized in membranes from the neostriatum and the subcortical limbic area. Neurotensin increased the KD but not the Bmax value of S(-)[N-propyl-3H(N)]propylnorapomorphine [( 3H]NPA) binding sites with a maximal increase of 20-40% at 3-10 nM of neurotensin in both areas. The KD increase was preferentially due to an increase in the dissociation rate. The maximal reduction of [3H]NPA binding (35%) was obtained within 5 min from the addition of neurotensin. Neurotensin increased the KH of dopamine vs [3H]raclopride binding and, in the presence of GTP, also KL. Neurotensin did not affect the percentage of binding sites in the high vs low affinity states or the binding characteristics of [3H]spiperone, [3H]SKF 38393, and [3H]SCH 23390. Serotonin (10 nM), neuropeptide Y (10 nM), Substance P (10 nM), dynorphin A (10 nM), morphine (10 nM), nicotine (100 nM), gamma-amino-n-butyric acid (1 microM), or N-methyl-D-aspartate (1 microM) did not affect [3H]NPA binding. These results indicate that neurotensin in vitro selectively reduces D2 agonist affinity by an enhancement of the dissociation rate. This antagonistic intramembrane interaction may underlie the neuroleptic-like effects of neurotensin at low concentrations in vivo on D2 agonist binding, dopamine release, and on D2-mediated behaviours.
journal_name
Brain Resjournal_title
Brain researchauthors
von Euler Gdoi
10.1016/0006-8993(91)90753-isubject
Has Abstractpub_date
1991-10-04 00:00:00pages
93-8issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(91)90753-Ijournal_volume
561pub_type
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