Comparison of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD)- and 1R,3S-ACPD-stimulated brain phosphoinositide hydrolysis.
(1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and (1R,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1R,3S-ACPD) were characterized for potency, efficacy, and selectivity at metabotropic excitatory amino acid receptors. 1S,3R-ACPD stimulated [3H]phosphoinositide hydrolysis in slices of the neonatal and adult rat hippocampus with full efficacy and twice the potency relative to what has been shown for (+/-)-trans-ACPD. 1S,3R-ACPD was up to 30 times more potent in activating metabotropic excitatory amino acid receptors, compared to its affinity for [3H]CGS19755 binding to NMDA receptors. In contrast, 1R,3S-ACPD was much less potent, efficacious, and selective than 1S,3R-ACPD. Although 1S,3R-ACPD is not specific, it is a most selective and efficacious agonist at metabotropic excitatory amino acid receptors.
Schoepp
D D
DD
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Johnson
B G
BG
True
R A
RA
Monn
J A
JA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000378:metabolism; D013268:Stimulation, Chemical; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D010716:Phosphatidylinositols; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid