Abstract
The role that the tridecapeptide neurotensin (NT) plays in the modulation of the aminoacidergic transmission is analyzed in different rat brain regions. NT exerts its effects through the activation of different receptor subtypes, NTR1, NTR2 and NTR3. The contribution of NTR1 receptor in modulating and reinforcing glutamate signalling will be shown including the involvement of interactions between NT and N-methyl-D-aspartate (NMDA) receptors. Extracellular accumulation of glutamate and the excessive activation of glutamate receptors, in particular NMDA receptors, is known to represent an important factor in the induction of glutamate-mediated neuronal damage occurring in Parkinsons disease and in pathologic events such as hypoxia and ischemia. An enhancing action of NT on glutamate-induced neurodegenerative effects is shown and NTR1 receptor antagonists could therefore become novel pharmaceutics in the treatment of neurodegenerative disease.
Keywords: Glutamate release, Glutamate-induced excitotoxicity, NMDA receptors, NTR1, Neurotensin receptor agonists and antagonists
Mini-Reviews in Medicinal Chemistry
Title: Emerging Evidence for Neurotensin Receptor 1 Antagonists as Novel Pharmaceutics in Neurodegenerative Disorders
Volume: 9 Issue: 12
Author(s): L. Ferraro, M. C. Tomasini, S. Beggiato, R. Guerrini, S. Salvadori, K. Fuxe, L. Calza, S. Tanganelli and T. Antonelli
Affiliation:
Keywords: Glutamate release, Glutamate-induced excitotoxicity, NMDA receptors, NTR1, Neurotensin receptor agonists and antagonists
Abstract: The role that the tridecapeptide neurotensin (NT) plays in the modulation of the aminoacidergic transmission is analyzed in different rat brain regions. NT exerts its effects through the activation of different receptor subtypes, NTR1, NTR2 and NTR3. The contribution of NTR1 receptor in modulating and reinforcing glutamate signalling will be shown including the involvement of interactions between NT and N-methyl-D-aspartate (NMDA) receptors. Extracellular accumulation of glutamate and the excessive activation of glutamate receptors, in particular NMDA receptors, is known to represent an important factor in the induction of glutamate-mediated neuronal damage occurring in Parkinsons disease and in pathologic events such as hypoxia and ischemia. An enhancing action of NT on glutamate-induced neurodegenerative effects is shown and NTR1 receptor antagonists could therefore become novel pharmaceutics in the treatment of neurodegenerative disease.
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Ferraro L., Tomasini C. M., Beggiato S., Guerrini R., Salvadori S., Fuxe K., Calza L., Tanganelli S. and Antonelli T., Emerging Evidence for Neurotensin Receptor 1 Antagonists as Novel Pharmaceutics in Neurodegenerative Disorders, Mini-Reviews in Medicinal Chemistry 2009; 9 (12) . https://dx.doi.org/10.2174/138955709789957495
DOI https://dx.doi.org/10.2174/138955709789957495 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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