Homocysteate-evoked release of acetylcholine from the rabbit retina.
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.
Sensory Sciences Center, Graduate School of Biomedical Sciences, UTHSC, Salt Lake City 84132, USA.
D M
DM
Linn
S C
SC
Massey
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000109:Acetylcholine / Q000378:metabolism*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013268:Stimulation, Chemical
D015763:2-Amino-5-phosphonovalerate; D000109:Acetylcholine; D000596:Amino Acids; D006710:Homocysteine; D008274:Magnesium; D018377:Neurotransmitter Agents; D011810:Quinoxalines; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C007956:homocysteic acid; C056723:FG 9041; C031231:2-amino-7-phosphonoheptanoic acid