Pharmacological characteristics of cyclic homologues of glycine at the N-methyl-D-aspartate receptor-associated glycine site.
In Xenopus oocytes, injected with mRNA from the brain of the rat, the characteristics of the cyclic homologues of glycine, ACPC, ACBC and cycloleucine have been examined. 1-Aminocyclopropane-1-carboxylate was a potent agonist at the NMDA-associated glycine site (EC50 = 0.09 +/- 0.02 microM) and exhibited characteristics consistent with a partial agonist. 1-Aminocyclobutane-1-carboxylate, in addition to its previously described antagonist properties, was found to possess agonist properties of low efficacy. Furthermore, ACBC did not completely block NMDA/glycine-induced currents, which is also consistent with partial agonist characteristics. In addition, small concentrations of glycine (less than 3 microM) did not alter the potency of ACBC, possibly suggesting that it is not simply a competitive glycine antagonist. Cycloleucine was a very weak glycine antagonist. These results suggest that as the size of the ring of cyclic homologues of glycine increases, there is a resulting transition from agonist to mixed agonist/antagonist to antagonist properties.
Watson
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Central Nervous System Diseases Research, G. D. Searle & Co., St Louis, Missouri 63198.
Lanthorn
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D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003515:Cycloleucine / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism*
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D011760:Pyrrolidinones; D012333:RNA, Messenger; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D003515:Cycloleucine; C016987:1-aminocyclobutanecarboxylic acid; C001369:1-hydroxy-3-amino-2-pyrrolidone; D005998:Glycine