Effect of Neurotensin on Dopamine and Muscarinic Acetylcholine Receptors in the Rat Striatum
Neurotensin (NT) is a tridecapeptide first isolated and sequenced from bovine hypothalamus in 1973 (1). This peptide has a wide distribution within central and peripheral tissues where it is present in both neuronal and endocrine structures (2). In the mammalian central nervous system, NT has been established as a candidate of neurotransmitter/neuromodulator. NT-containing fibers (3,4) and NT receptors (5,6) have been observed in high density within the striatum. An interaction between dopamine and NT has been well demonstrated in the nigro-striatal neuronal pathway. For instance, it has been reported that NT receptors are not only located on dopaminergic perikarya and dendrites (7) but also on dopaminegic nerve terminals (8). In addition, NT facilitates endogenous or K+-evoked dopamine release (9,10,11). From receptor binding assay, it has been observed that NT decreases the affinity of D2 receptor agonist binding (12). On the other hand, NT dose not modulate the binding characteristics of 3H-spiperone, which is a D2 receptor antagonist (13).
KeywordsDopamine Receptor Agonist Binding High Affinity Binding Site Saturation Experiment Antagonist Binding
Unable to display preview. Download preview PDF.
- 2.C. B. Nemeroff, D. Luttinger, and A. J. Prange, Neurotensin and bombesin, in: “Handbook of Psychopharmacology”, L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds., Plenum Press, New York, p. 363 (1983)Google Scholar
- 12.G. Euler and K. Fuxe, Neurotensin reduces the affinity of D-2 dopamine receptors in rat striatal membranes, Acta Physiol. Scand., 131: 625 (1987)Google Scholar
- 13.C. B. Nemeroff, D. Luttinger, D. E. Hernandez, R. B. Mailman, G. A. Mason, S. D. Davis, E. Widerlov, G. D. Frye, C. A. Kilts, K. Beaumont, G. R. Breese, and A. J. Prange, Interactions of neurotensin with brain dopamine systems: biochemical and behavioral studies, J. Pharmacol. Exp. Ther., 225: 337 (1983)PubMedGoogle Scholar
- 14.S. E. Leff and I. Creese, Dopamine receptors re-explained, Trends Pharmacol. Sci., 463 (1983)Google Scholar
- 16.L. C. lorio, A. Barnett, F. H. Leits, V. P. Houser, and C. A. Korduba, SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems, J. Pharmacol. Exp. Ther., 226: 462 (1983)Google Scholar
- 20.P. Seeman, C. Ulpian, D. Grigoriadis, I. Pri-Bar, and 0. Buchman, Conversion of dopamine D1 receptors from high to low affinity for dopamine, Biochem. Pharmacol., 34: 151 (1985)Google Scholar
- 27.D. M. Jackson and M. Hashizume, Bromocriptine induces marked locomotor stimulation in dopamine-depleted mice when D-1 dopamine receptors are stimulated with SK&F 38393, Psychopharmacol., 90: 147 (1986)Google Scholar
- 29.K. S. Kanba and E. Richelson, Comparison of the stimulation of inositol phospholipid hydrolysis and of cyclic GMP formation by neurotensin, some of its analogs, and neuromedin N in neuroblastoma clone N1E-115, Biochem. Pharmacol., 36: 869 (1987)Google Scholar