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Homocysteic Acid as a Putative Excitatory Amino Acid Neurotransmitter: I. Postsynaptic Characteristics at N ‐Methyl‐D‐Aspartate‐Type Receptors on Striatal Cholinergic Interneurons
Author(s) -
Lehmann John,
Tsai Cindy,
Wood Paul L.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb01157.x
Subject(s) - nmda receptor , excitatory postsynaptic potential , tachyphylaxis , chemistry , cholinergic , acetylcholine , neurotransmitter , agonist , biology , receptor , medicine , endocrinology , biochemistry
The actions of the stereoisomers of homocysteic acid (HCA) were characterized at N ‐methyl‐D‐aspartate (NMDA)‐type receptors which mediate excitatory amino acid‐evoked [ 3 H]acetylcholine ([ 3 H]ACh) release from striatal cholinergic interneurons. Like NMDA, l‐HCA and d‐HCA evoked the release of [ 3 H]ACh formed from [ 3 H]choline in striatal slices. The concentration‐response curve for l‐HCA was virtually superimposable on that for NMDA, yielding an equal EC 50 value (56.1 μ M ) and maximal response. However, d‐HCA was weaker, with an EC 50 value of 81.1 μ M , and an apparently smaller maximal response. l‐HCA‐evoked [ 3 H]ACh release was inhibited by the same categories of compounds which inhibit NMDA‐evoked [ 3 H]ACh release: the divalent ion Mg 2+ (IC 50 = 25.8 μ M ); competitive NMDA antagonists 2‐amino‐7‐phosphonoheptanoate (IC 50 = 51.2 μ M ) and 3‐(2‐carboxypiperazin‐4‐yi)propyl‐1 ‐phosphonic acid (IC 50 = 20.1 μ M ); and the dissociative anesthetics tile‐tamine (IC 50 = 0.59 μ M ) and MK‐801 (IC 50 = 0.087 μ M ). Like NMDA, l‐HCA produced a tachyphylaxis in this system. Tachyphylaxis to NMDA resulted in a decreased response to l‐HCA, and conversely, tachyphylaxis to l‐HCA resulted in a decreased response to NMDA. The results suggest that l‐HCA is an agonist at the NMDA‐type receptor and may represent an endogenous ligand for this excitatory amino acid receptor.