Presynaptic modulation of glutamate and dynorphin release by excitatory amino acids in the guinea-pig hippocampus.
Excitatory amino acid agonists and antagonists were evaluated for their ability to affect the concomitant release of endogenous L-glutamate and dynorphin A(1-8)-like immunoreactivity from guinea-pig hippocampal mossy fiber synaptosomes. Previous work in this laboratory demonstrated that L(+)2-amino-4-phosphonobutyrate inhibits the potassium-evoked release of these endogenous neurotransmitters from guinea-pig but not rat hippocampal mossy fiber synaptosomes. Therefore, the present study was conducted to evaluate excitatory amino acid agonists as indices to the functional properties of this L(+)2-amino-4-phosphonobutyrate-sensitive glutamatergic autoreceptor on mossy fiber terminals. Low micromolar concentrations of quisqualate, but not kainate, N-methyl-D-aspartate, nor RS-alpha-amino-3-hydroxy-5-methyl-4-isoazole-propionic acid, significantly inhibited the potassium-evoked release of both L-glutamate and dynorphin A(1-8)-like immunoreactivity. Quisqualate-induced inhibition of L-glutamate release from mossy fiber terminals was antagonized by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. In contrast, high concentrations of kainate enhanced the potassium-evoked release of L-glutamate and dynorphin A(1-8)-like immunoreactivity, and this potentiation was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. Kainate (1 mM) was the only agonist which significantly enhanced the basal release of L-glutamate, whereas the spontaneous efflux of dynorphin A(1-8)-like immunoreactivity was not affected by any of the agonists tested. The results presented in this paper suggest the existence of inhibitory and excitatory presynaptic glutamatergic autoreceptors that act to modulate the release of endogenous L-glutamate- and prodynorphin-derived peptides from guinea-pig hippocampal mossy fiber terminals. These inhibitory and excitatory autoreceptors, which are sensitive to quisqualate/L(+)2-amino-4-phosphonobutyrate or kainate, respectively, may play an important role in regulating synaptic activity at glutamatergic synapses throughout the central nervous system.
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, NC 27858.
R L
RL
Gannon
D M
DM
Terrian
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism* / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D011810:Quinoxalines; D007051:Ibotenic Acid; D001224:Aspartic Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D004399:Dynorphins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D011188:Potassium; D007608:Kainic Acid