Homocysteic Acid as a Putative Excitatory Amino Acid Neurotransmitter: I. Postsynaptic Characteristics at N‐Methyl‐D‐Aspartate‐Type Receptors on Striatal Cholinergic Interneurons

Publisher Website
Google Scholar
Abstract
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 [3H]acetylcholine ([3H]ACh) release from striatal cholinergic interneurons. Like NMDA, l‐HCA and d‐HCA evoked the release of [3H]ACh formed from [3H]choline in striatal slices. The concentration‐response curve for l‐HCA was virtually superimposable on that for NMDA, yielding an equal EC50 value (56.1 μM) and maximal response. However, d‐HCA was weaker, with an EC50 value of 81.1 μM, and an apparently smaller maximal response. l‐HCA‐evoked [3H]ACh release was inhibited by the same categories of compounds which inhibit NMDA‐evoked [3H]ACh release: the divalent ion Mg2+ (IC50= 25.8 μM); competitive NMDA antagonists 2‐amino‐7‐phosphonoheptanoate (IC50= 51.2 μM) and 3‐(2‐carboxypiperazin‐4‐yi)propyl‐1 ‐phosphonic acid (IC50= 20.1 μM); and the dissociative anesthetics tile‐tamine (IC50= 0.59 μM) and MK‐801 (IC50= 0.087 μM). 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.

This publication has 16 references indexed in Scilit: