In vitro release and electrophysiological effects in situ of homocysteic acid, an endogenous N-methyl-(D)-aspartic acid agonist, in the mammalian striatum.
A potassium-induced, calcium-dependent release of endogenous homocysteic acid (HCA) from rat striatal slices was demonstrated. A precolumn derivatization high-performance liquid chromatography method was developed that allowed quantitative determination of sulfur-containing amino acids at the picomole level. Intracellular recordings from cat caudate neurons during simultaneous microiontophoretic application of drugs and electrical stimulation of the corticocaudate pathway showed that (L)-HCA evoked a depolarization pattern similar to that induced by N-methyl-(D)-aspartic acid (NMDA), and both these depolarizations could be selectively inhibited by a specific NMDA antagonist, (D)-2-amino-7-phosphonoheptanoic acid [(D)-AP-7]. A selective antagonism of (L)-HCA-induced depolarizations by (D)-AP-7 was confirmed in quantitative experiments with the frog hemisected spinal cord in vitro. Small quantities of iontophoretically applied (L)-HCA, but not of quisqualate, potentiated cortically evoked EPSPs in cat caudate neurons. These observations suggest that (L)-HCA might be a candidate as an NMDA-receptor-preferring endogenous transmitter in the caudate nucleus. One possible function for such transmitter systems could be the enhancement of EPSPs.
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007478:Iontophoresis; D010069:Oxadiazoles / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D016318:Quisqualic Acid; D011896:Rana temporaria; D051381:Rats; D014702:Veratrine / Q000494:pharmacology
D005971:Glutamates; D010069:Oxadiazoles; D006710:Homocysteine; C007956:homocysteic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D016318:Quisqualic Acid; D014702:Veratrine; D011188:Potassium; D002118:Calcium