fg-9041 and homocysteic-acid

The cholinergic amacrine cells of the rabbit retina can be labeled with [3H]choline and the activity of the cholinergic population monitored by following the release of [3H]acetylcholine. It has been proposed that L-homocysteate may be the main endogenous transmitter released onto cholinergic amacrine cells by bipolar cells. Therefore, we have examined the effects of the isomers of homocysteate on the release of [3H]acetylcholine. In magnesium-free medium, D-homocysteate was slightly more potent than the L-isomer. The addition of magnesium, which blocks responses mediated by NMDA receptors, preferentially reduced but did not eliminate, the response to L-homocysteate. 2-Amino-7-phosphonoheptanoate, a potent NMDA antagonist, preferentially blocked L-homocysteate evoked responses. 6,7-Dinitroquinoxaline-2,3-dione, a potent kainate antagonist, preferentially blocked D-homocysteate-evoked responses. Therefore, in the rabbit retina, L-homocysteate is an NMDA-preferring agonist, whereas D-homocysteate is a kainate-preferring agonist. In addition, we found that L-homocysteate can activate the physiologically activated kainate receptor but only when used in millimolar concentrations and under conditions that minimize NMDA-receptor activation. However, the low potency of L-homocysteate combined with low affinity for the glutamate transporter, lack of immunocytochemical localization in bipolar cells, and low retinal content place serious limitations on the role of L-homocysteate at the bipolar-to-cholinergic amacrine cell synapse.

Topics: 2-Amino-5-phosphonovalerate; Acetylcholine; Amino Acids; Animals; Homocysteine; Magnesium; Neurotransmitter Agents; Quinoxalines; Rabbits; Receptors, Kainic Acid; Receptors, N-Methyl-D-Aspartate; Retina; Stereoisomerism; Stimulation, Chemical

Co-effects of microelectrophoretic application of 2-amino-5-phosphonovalerate (APV), ketamine, 6,7-dinitroqinoxaline-2,3-dione (DNQX), kynurenate (Kyn) and spantide on 34 spinal dorsal horn neurons were studied. Co-application of spantide and APV or DNQX produced a synergetic inhibition of responses by tibial stimulation in 10/23 and 3/8 neurons, respectively, and also in 3/8 neurons by administration of DL-sodium homocysteate. Spantide enhanced APV- or ketamine-induced inhibition of C responses of 8/19 neurons to sural stimulation, DNQX induced that of 2/4 neurons to gastrocnemius-soleous stimulation (GS), and Kyn induced that to both sural (8/19) and GS (2/4). The results suggest an interaction of SP and NMDA, non-NMDA receptors in processing spinal nociception.

Topics: 2-Amino-5-phosphonovalerate; Animals; Cats; Electric Stimulation; Homocysteine; Ketamine; Kynurenic Acid; Muscles; Neurokinin-1 Receptor Antagonists; Neurons; Nociceptors; Quinoxalines; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Neurokinin-1; Spinal Cord; Substance P; Sural Nerve

The role of the sulphur-containing amino acids (SAAs) in the initiation of fictive locomotion was tested in an isolated spinal cord preparation from newborn rats. These substances were bath-applied and the fictive locomotion was recorded in the lumbar ventral roots. It emerged from this study that all the compounds tested could trigger an organized pattern (alternating left and right bursts of activity) with a dose-dependent response. However, specific frequency and concentration ranges were observed with each of these SAAs. Moreover, a clear-cut difference between D and L isomers in the ability of the SAAs to induce this activity was observed; the SAAs of the D-forms were found to be generally more potent than those of the L-forms. The effects of the SAAs were found to be mediated by both NMDA and non-NMDA receptors, since they were blocked in a dose-dependent manner by the specific antagonists of these receptors. Moreover, it was observed that beta-p-chlorophenylglutamic acid, an uptake inhibitor of homocysteic acid (HCA), potentiated the effect of exogenously applied HCA, which supports the idea that HCA may act as a transmitter. The sulphuric and non-sulphuric amino acids were also classified in their order of potency. The most potent compound turned out to be D-homocysteine sulphinic acid, while D-cysteine sulphinic acid was the least potent. It also emerged that the maximal frequencies obtained with SAAs and excitatory amino acids were in the same range, which might correspond to the maximal limits of this system.

Topics: Amino Acids; Amino Acids, Sulfur; Animals; Animals, Newborn; Dose-Response Relationship, Drug; Homocysteine; In Vitro Techniques; Motor Activity; Quinoxalines; Rats; Rats, Wistar; Receptors, Amino Acid; Receptors, N-Methyl-D-Aspartate; Spinal Cord