METABOTROPIC GLUTAMATE RECEPTOR ACTIVATION CONTRIBUTES TO NOCICEPTIVE REFLEX ACTIVITY IN THE RAT SPINAL CORD IN VITRO
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EXPERIMENTAL PROCEDURES
Hemisected spinal cords were prepared as described previously 31, 34 from 10–14-day-old Sprague-Dawley rat pups (weight 24–26 g) born in-house. Following Enflurane anaesthesia, animals were killed by decapitation and spinal cords removed and placed into aerated (95% O2 and 5% CO2) and cooled artificial cerebrospinal fluid (ACSF in mM; 138 NaCl; 3.35 KCl; 21.0 NaHCO3; 0.58 NaH2PO4; 10.0 glucose; 1.16 MgCl2; 1.26 CaCl2; pH 7.4). Spinal cords were hemisected and transferred to a recording chamber
RESULTS
The selective mGluR agonist, (1 S,3 R)-ACPD, superfused to the spinal cord for 30 s, produced reproducible and dose-dependent ventral root depolarizations (ec50 = 58 ± 7 μM; n = 4; Fig. 1).
The potency of selective mGluR and ionotropic receptor antagonists was subsequently determined against concentrations of agonists which evoked submaximal ventral root responses [NMDA: 100 μM; [33] (1 S,3 R)-ACPD: 100 μM]. NMDA-induced ventral root responses were blocked by submaximal concentrations of d-AP5
DISCUSSION
In the present study we have examined the contribution of mGluR activation to the nociceptive segmental reflex in isolated spinal cords prepared from rat pups (10–14 days old), and compared the contribution of mGluR with NMDA receptor activation.
Ventral root responses measured after dorsal root stimulation are complex events which involve the release of neuropeptides and excitatory amino acids, and activation of postsynaptic receptors. [31] It has been determined previously that both ionotropic
CONCLUSION
In addition to d-AP5, MCPG is also effective in reducing C-fibre-induced ventral root responses, hence mGluR and NMDA receptor activation are involved in the generation of the segmental nociceptive reflex.
References (41)
- et al.
Phenylglycine derivatives as new pharmacological tools for investigating the role of metabotropic glutamate receptors in the central nervous system
Neuroscience
(1993) - et al.
Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid
Neurosci. Lett.
(1992) - et al.
2-Amino-5-phosphonovalerate (2APV), a potent and selective antagonist of amino acid-induced and synaptic excitation
Neurosci. Lett.
(1981) - et al.
Evidence for involvement of N-methylaspartate receptors in “windup” of class 2 neurones in the dorsal horn of the rat
Brain Res.
(1987) - et al.
Competitive antagonism at metabotropic glutamate receptors by (S)4-carboxyphenylglycine and (RS)-α-methyl-4-carboxyphenylglycine
Eur. J. Pharmac.
(1993) - et al.
Potentiation of cAMP responses by metabotropic glutamate receptors depresses excitatory synaptic transmission by a kinase-independent mechanism
Neuron
(1994) - et al.
Stereospecific antagonism by (+)-α-methyl-4-carboxyphenylglycine (MCPG) of (1S,3R)-ACPD-induced effects in neonatal rat motoneurones and rat thalamic neurones
Neuropharmacology
(1993) - et al.
Interactions between metabotropic and ionotropic glutamate receptor agonists in the rat spinal cord in vitro
Neuropharmacology
(1995) - et al.
The role of neurokinin and N-methyl- d-aspartate receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro
Neuroscience
(1993) - et al.
Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization
Neuroscience
(1994)
Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat
Neuroscience
The metabotropic glutamate receptors: structure and functions
Neuropharmacology
Get receptive to metabotropic glutamate receptors
Curr. Opin. Neurobiol.
Long duration ventral root potentials in the neonatal rat spinal cord in vitro; the effects of ionotropic and metabotropic excitatory amino acid receptor antagonists
Brain Res.
Contribution of NK1 and NK2 receptor activation to high threshold afferent fibre evoked ventral root responses in the rat spinal cord in vitro
Brain Res.
No evidence for contribution of nitric oxide to spinal reflex activity in the rat spinal cord in vitro
Neurosci. Lett.
Synaptic activation of dorsal horn neurons by selective C-fibre excitation with capsaicin in the mouse spinal cord in vitro
Neuroscience
Tachykinin induced regulation of excitatory amino acid responses in the rat spinal cord in vitro
Neurosci Lett.
Modulation of spinal excitability: co-operativity between neurokinins and excitatory amino acid neurotransmitters
Trends Neurosci.
Phenylglycine derivatives as antagonists of metabotropic glutamate receptors
Trends pharmac. Sci.
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Present address: Division of Physiology, UMDS, St. Thomas' Campus, Lambeth Palace Rd, London SE1 7EH, U.K.