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Pharmacology of metabotropic glutamate receptor-mediated enhancement of responses to excitatory and inhibitory amino acids on rat spinal neurones in vivo.

Abstract：

:Using the technique of microelectrophoresis on spinal neurones in pentobarbitone-anaesthetized rats, (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylate (1S,3R-ACPD) reversibly and dose-dependently enhanced responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), kainate, N-methyl-D-aspartate (NMDA) and L-glutamate to a similar extent. 1S,3R-ACPD also enhanced inhibitory responses to both glycine and gamma-aminobutyrate (GABA). Such results are consistent with a metabotropic glutamate receptor-mediated decrease in membrane conductance. 1S,3R-ACPD was the most active metabotropic agonist tested for these effects; the rank order of activity was: 1S,3R-ACPD > or = (2S,3S,4S)alpha-(carboxycyclopropyl)-glycine(L-CCG-l) > (R, S)-3,5-dihydroxy-phenylglycine (3,5-DHPG) > (S)-homoquisqualate > quisqualate = 1S,3S-ACPD > L-2-amino-4-phosphonobutyrate (L-AP4) > 1R,3S-ACPD. These effects of 1S,3R-ACPD were antagonized by (RS)-alpha-methyl-4-carboxy-phenylglycine (M4CPG) and (S)-4-carboxy-3-hydroxy-phenylglycine (4C3HPG) but not by (S)-4-carboxy-phenylglycine (4CPG) or L-amino-3-phosphono-propionate (L-AP3). The pharmacology of the actions of mGluR agonists and antagonists on rat spinal neurones in vivo does not obviously correlate with the published pharmacology of a single cloned metabotropic glutamate receptor subtype but rather suggests that both Group 1 and 2 receptors contribute to the above effects.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Bond A,Lodge D

doi

10.1016/0028-3908(95)00046-9

subject

Has Abstract

pub_date

1995-08-01 00:00:00

pages

1015-23

issue

8

eissn

0028-3908

issn

1873-7064

pii

0028390895000469

journal_volume

34

pub_type

杂志文章

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