TY - JOUR
T1 - Neurotensin selectively facilitates glutamatergic transmission in globus pallidus
AU - Chen, L.
AU - YUNG, Kin Lam
AU - Yung, W. H.
N1 - Funding Information:
The authors wish to thank Dr. Danielle Gully (Sanofi Recherche, France) for kindly providing SR48692 and SR142948A. This work was supported by the National Natural Science Foundation of China (30470545 to L. Chen) and the Research Grants Council of Hong Kong (CUHK 4175/02M to W. H. Yung).
PY - 2006/9
Y1 - 2006/9
N2 - 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 μM significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABAA 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-[[17β-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.
AB - 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 μM significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABAA 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-[[17β-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.
KW - globus pallidus
KW - neurotensin
KW - postsynaptic currents
UR - http://www.scopus.com/inward/record.url?scp=33747202699&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2006.05.049
DO - 10.1016/j.neuroscience.2006.05.049
M3 - Journal article
C2 - 16814931
AN - SCOPUS:33747202699
SN - 0306-4522
VL - 141
SP - 1871
EP - 1878
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -