Neurotensin selectively facilitates glutamatergic transmission in globus pallidus.
The tridecapeptide neurotensin has been demonstrated to modulate neurotransmission in a number of brain regions. There is evidence that neurotensin receptors exist in globus pallidus presynaptically and postsynaptically. Whole-cell patch-clamp recordings were used to investigate the modulatory effects of neurotensin on glutamate and GABA transmission in this basal ganglia nucleus in rats. Neurotensin at 1 microM significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABA(A) receptor-mediated miniature inhibitory postsynaptic currents. The presynaptic facilitation of neurotensin on glutamatergic transmission could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). The selective neurotensin type-1 receptor antagonist, SR48692 {2-[(1-(7-chloro-4-quinolinyl)-5-2(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino]-tricyclo(3.3.1.1.(3.7))-decan-2-carboxylic acid}, blocked this facilitatory effect of neurotensin, and which itself had no effect on miniature excitatory postsynaptic currents. The specific phospholipase C inhibitor, U73122 {1-[6-[[17beta-3-methoyyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione}, significantly inhibit neurotensin-induced facilitation on glutamate release. Taken together with the reported postsynaptic depolarization of neurotensin in globus pallidus, it is suggested that neurotensin excites the globus pallidus neurons by multiple mechanisms which may provide a rationale for further investigations into its involvement in motor disorders originating from the basal ganglia.
Chen
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Department of Physiology, The Chinese University of Hong Kong, Shatin, Hong Kong, China. chenleiqd@163.com
Yung
K K L
KK
Yung
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WH
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000166:cytology*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009496:Neurotensin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011720:Pyrazoles / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D004963:Estrenes; D018756:GABA Antagonists; D011720:Pyrazoles; D011760:Pyrrolidinones; D011804:Quinolines; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C079087:SR 48692; D009496:Neurotensin; D018698:Glutamic Acid; D013779:Tetrodotoxin; D001640:Bicuculline