REQUIREMENT OF METABOTROPIC GLUTAMATE RECEPTORS FOR THE GENERATION OF INFLAMMATION-EVOKED HYPEREXCITABILITY IN RAT SPINAL-CORD NEURONS

被引:152
作者
NEUGEBAUER, V [1 ]
LUCKE, T [1 ]
SCHAIBLE, HG [1 ]
机构
[1] UNIV WURZBURG, DEPT PHYSIOL, D-97070 WURZBURG, GERMANY
关键词
JOINT NOCICEPTION; L-2-AMINO-3-PHOSPHONOPROPIONIC ACID; TRANS-(+/-)-1-AMINO-(1S; 3R)-CYCLOPENTANE-DICARBOXYLIC ACID;
D O I
10.1111/j.1460-9568.1994.tb00616.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the central nervous system the transmitter L-glutamate activates both ionotropic receptors coupled to cation channels and metabotropic receptors coupled to G-proteins. The role of metabotropic receptors in the processing of mechanosensory and nociceptive information was studied in a subset of spinal cord neurons with afferent input from the knee joint in anaesthetized rats using electrophysiological methods. The ionophoretic administration of L-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist at the metabotropic receptor, had no effect on the responses to innocuous and noxious pressure applied to the normal knee joint, although the antagonist prevented the potentiation of these responses evoked by the ionophoretic administration of a specific agonist at the metabotropic receptor, trans-(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid (t-ACPD). By contrast, in neurons that were rendered hyperexcitable by acute inflammation in the knee joint L-AP3 reduced the responses to pressure applied to the knee. When L-AP3 was applied during induction of inflammation and throughout the subsequent 1.5 h the spinal neurons did not develop hyperexcitability over this time period. L-AP3 did not impair the activation of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA receptors by the specific agonists. We conclude that spinal metabotropic glutamate receptors are not involved in the mediation of responses to innocuous and noxious mechanical stimuli applied under normal conditions. They are required, however, for the generation of inflammation-evoked hyperexcitability of spinal cord neurons, a form of functional plasticity underlying the painfulness in pathophysiological conditions such as inflammation.
引用
收藏
页码:1179 / 1186
页数:8
相关论文
共 53 条
[1]   QUISQUALATE METABOTROPIC RECEPTORS MODULATE NMDA CURRENTS AND FACILITATE INDUCTION OF LONG-TERM POTENTIATION THROUGH PROTEIN-KINASE-C [J].
ANIKSZTEJN, L ;
OTANI, S ;
BENARI, Y .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1992, 4 (06) :500-505
[2]   SIGNAL TRANSDUCTION AND PHARMACOLOGICAL CHARACTERISTICS OF A METABOTROPIC GLUTAMATE RECEPTOR, MGLUR1, IN TRANSFECTED CHO CELLS [J].
ARAMORI, I ;
NAKANISHI, S .
NEURON, 1992, 8 (04) :757-765
[3]   INDUCTION OF LTP IN THE HIPPOCAMPUS NEEDS SYNAPTIC ACTIVATION OF GLUTAMATE METABOTROPIC RECEPTORS [J].
BASHIR, ZI ;
BORTOLOTTO, ZA ;
DAVIES, CH ;
BERRETTA, N ;
IRVING, AJ ;
SEAL, AJ ;
HENLEY, JM ;
JANE, DE ;
WATKINS, JC ;
COLLINGRIDGE, GL .
NATURE, 1993, 363 (6427) :347-350
[4]   INOSITOL PHOSPHATES AND CELL SIGNALING [J].
BERRIDGE, MJ ;
IRVINE, RF .
NATURE, 1989, 341 (6239) :197-205
[5]   PHENYLGLYCINE DERIVATIVES AS NEW PHARMACOLOGICAL TOOLS FOR INVESTIGATING THE ROLE OF METABOTROPIC GLUTAMATE RECEPTORS IN THE CENTRAL-NERVOUS-SYSTEM [J].
BIRSE, EF ;
EATON, SA ;
JANE, DE ;
JONES, PLS ;
PORTER, RHP ;
POOK, PCK ;
SUNTER, DC ;
UDVARHELYI, PM ;
WHARTON, B ;
ROBERTS, PJ ;
SALT, TE ;
WATKINS, JC .
NEUROSCIENCE, 1993, 52 (03) :481-488
[6]  
BLEAKMAN D, 1992, MOL PHARMACOL, V42, P192
[7]   A SYNAPTIC MODEL OF MEMORY - LONG-TERM POTENTIATION IN THE HIPPOCAMPUS [J].
BLISS, TVP ;
COLLINGRIDGE, GL .
NATURE, 1993, 361 (6407) :31-39
[8]   ACTIVATION OF GLUTAMATE METABOTROPIC RECEPTORS INDUCES LONG-TERM POTENTIATION [J].
BORTOLOTTO, ZA ;
COLLINGRIDGE, GL .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 214 (2-3) :297-298
[9]   SUBTYPES OF METABOTROPIC EXCITATORY AMINO-ACID RECEPTOR DISTINGUISHED BY STEREOISOMERS OF THE RIGID GLUTAMATE ANALOG, 1-AMINOCYCLOPENTANE-1,3-DICARBOXYLATE [J].
CARTMELL, J ;
CURTIS, AR ;
KEMP, JA ;
KENDALL, DA ;
ALEXANDER, SPH .
NEUROSCIENCE LETTERS, 1993, 153 (01) :107-110
[10]   MODULATION OF AMPA AND NMDA RESPONSES IN RAT SPINAL DORSAL HORN NEURONS BY TRANS-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLIC ACID [J].
CERNE, R ;
RANDIC, M .
NEUROSCIENCE LETTERS, 1992, 144 (1-2) :180-184