Presynaptic mGlu1 type receptors potentiate transmitter output in the rat cortex.
In the present study we used freely moving rats with a microdialysis probe placed in their parietal cortex to study the effects of local application of agonists and antagonists of metabotropic glutamate (mGlu) receptors on glutamate release. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 0.1-1 mM), a non-selective agonist of metabotropic glutamate (mGlu) receptors, increased glutamate concentration in the dialysate up to 3-fold. A significant increase in glutamate output in cortical dialysates was also obtained with (RS)-3,5-dihydroxyphenylglycine (DHPG; 0.5-1 mM), a group 1-selective mGlu receptor agonist, suggesting the involvement of group 1 mGlu receptors in 1S,3R-ACPD effects. S-4-carboxyphenylglycine (S-4CPG; 0.3 microM), a mGlu1 receptor antagonist with a mild agonist action on mGlu2 receptors, antagonised, in a surmountable manner, the effects of 1S,3 R-ACPD. Similarly, 1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.03-1 mM) a selective group 1 antagonist with a preferential action on mGlu1 type receptors, antagonised the effects of 1S,3R-ACPD. Finally, (S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)-glycine (UPF596; 30-300 microM), a potent mGlu1 antagonist with modest agonist activity on mGlu5, antagonised 1S,3R-ACPD-induced glutamate release. In conclusion, our data showed that 1S,3R-ACPD-induced glutamate release in the parietal cortex is mediated by mGlu1 receptors and that, under basal conditions, these receptors are not tonically activated.
Moroni
F
F
Dipartimento di Farmacologia Preclinica e Clinica della Università di Firenze, Italy. moronif@stat.ds.unifi.it
Cozzi
A
A
Lombardi
G
G
Sourtcheva
S
S
Leonardi
P
P
Carfì
M
M
Pellicciari
R
R
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D017551:Microdialysis; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology
C095756:1-aminoindan-1,5-dicarboxylic acid; D001565:Benzoates; D001643:Bridged Bicyclo Compounds; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; D012118:Resorcinols; C100726:UPF 596; C104077:metabotropic glutamate receptor type 1; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; C079693:4-carboxyphenylglycine; D005998:Glycine