Evaluation of agonists and antagonists acting at Group I metabotropic glutamate receptors in the thalamus in vivo

被引:23
作者
Salt, TE
Turner, JP
Kingston, AE
机构
[1] UCL, Inst Ophthalmol, London EC1V 9EL, England
[2] Lilly Res Ctr Ltd, Windlesham GU20 6PH, Surrey, England
关键词
thalamus; mGlu1; mGlu5; metabotropic glutamate receptor antagonist; LY367366; LY367385; LY393053; 1-aminoindan-1,5-dicarboxylic acid;
D O I
10.1016/S0028-3908(99)00081-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Recordings were made from single neurones in the ventrobasal thalamus of anaesthetised rats in order to evaluate the properties of several agonists and antagonists of Group I mGlu receptors. The selective mGlu1 receptor antagonist LY367385 was found to reduce excitatory responses to iontophoretically applied ACPD and DHPG whereas the mGlu5 agonist CHPG was resistant to antagonism. The antagonists LY367366 and LY393053 reduced responses to all three agonists, but without reducing responses to NMDA or AMPA. Although AIDA was also found to reduce mGlu agonist-evoked responses, this antagonist also produced significant reductions in responses to NMDA and AMPA. These data suggest that there are functional mGlu1 and mGlu5 receptors in the thalamus. Furthermore, LY367385 is a useful tool for investigating mGlu1 functions whereas LY367366 and LY393053 have a broader spectrum of action. The usefulness of AIDA as an antagonist in physiological experiments would appear to be limited by its effects against NMDA and AMPA. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1505 / 1510
页数:6
相关论文
共 23 条
[1]  
ABE T, 1992, J BIOL CHEM, V267, P13361
[2]  
BAKER SR, 1998, SOC NEUR ABSTR, V28
[3]   Neuroprotective activity of the potent and selective mGlula metabotropic glutamate receptor antagonist, (+)-2-methyl-4 caroxyphenylglycine (LY367385): comparison with LY357366, a broader spectrum antagonist with equal affinity for mGlula and mGlu5 receptors [J].
Bruno, V ;
Battaglia, G ;
Kingston, A ;
O'Neill, MJ ;
Catania, MV ;
Di Grezia, R ;
Nicoletti, F .
NEUROPHARMACOLOGY, 1999, 38 (02) :199-207
[4]   (+)-2-methyl-4-carboxyphenylglycine (LY367385) selectively antagonises metabotropic glutamate mGluR1 receptors [J].
Clark, BP ;
Baker, SR ;
Goldsworthy, J ;
Harris, JR ;
Kingston, AE .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (21) :2777-2780
[5]   Pharmacology and functions of metabotropic glutamate receptors [J].
Conn, PJ ;
Pin, JP .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1997, 37 :205-237
[6]   Direct effects of metabotropic glutamate receptor compounds on native and recombinant N-methyl-D-aspartate receptors [J].
Contractor, A ;
Gereau, RW ;
Green, T ;
Heinemann, SF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8969-8974
[7]   (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) activates mGlu(5), but not mGlu(1), receptors expressed in CHO cells and potentiates NMDA responses in the hippocampus [J].
Doherty, AJ ;
Palmer, MJ ;
Henley, JM ;
Collingridge, GL ;
Jane, DE .
NEUROPHARMACOLOGY, 1997, 36 (02) :265-267
[8]   MEDIATION OF THALAMIC SENSORY RESPONSES INVIVO BY ACPD-ACTIVATED EXCITATORY AMINO-ACID RECEPTORS [J].
EATON, SA ;
BIRSE, EF ;
WHARTON, B ;
SUNTER, DC ;
UDVARHELYI, PM ;
WATKINS, JC ;
SALT, TE .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1993, 5 (02) :186-189
[9]   Endogenous activation of metabotropic glutamate receptors contributes to burst frequency regulation in the lamprey locomotor network [J].
Krieger, P ;
Grillner, S ;
El Manira, A .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1998, 10 (11) :3333-3342
[10]   CELLULAR-LOCALIZATION OF A METABOTROPIC GLUTAMATE RECEPTOR IN RAT-BRAIN [J].
MARTIN, LJ ;
BLACKSTONE, CD ;
HUGANIR, RL ;
PRICE, DL .
NEURON, 1992, 9 (02) :259-270