Inhibition of forskolin-stimulated cyclic AMP formation by 1-aminocyclopentane-trans-1,3-dicarboxylate in guinea-pig cerebral cortical slices.
The effects of the selective metabotropic glutamate receptor agonist 1-aminocyclopentane-trans-1,3-dicarboxylate (t-ACPD) on forskolin-stimulated cyclic AMP formation in guinea-pig cerebral cortex slices were determined. t-ACPD inhibited the accumulation of [3H]cyclic AMP by approximately 80%, with an IC50 value of 35 +/- 4 microM. The effect was reversible and stereoselective, with the 1S,3R isomer being approximately 400-fold more potent than the 1R,3S isomer. L-Glutamate (over a restricted concentration range) also partially inhibited the response to forskolin, but quisqualate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and N-methyl-D-aspartate (NMDA) were ineffective. The effect of t-ACPD was not blocked by antagonists of the phospholipase C-linked metabotropic glutamate receptor, the AMPA ionotropic glutamate receptor, or the NMDA receptor. In summary, our results indicate the presence of a glutamate receptor in guinea-pig brain that is activated selectively by t-ACPD and that is negatively linked to adenylyl cyclase.
Cartmell
J
J
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, England.
Kemp
J A
JA
Alexander
S P
SP
Hill
S J
SJ
Kendall
D A
DA
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology; D013237:Stereoisomerism
D000596:Amino Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D005576:Colforsin; D000242:Cyclic AMP