Regulation of glutamate release via NMDA and 5-HT1A receptors in guinea pig dentate gyrus.
The regulation by 5-HT1A and N-methyl-D-aspartate (NMDA) receptors on the endogenous glutamate release was investigated in slices of guinea pig dentate gyrus. The release of glutamate was increased dose-dependently by the 5-HT1A receptor antagonist, NAN-190 at 0.01 to 300 nM, but was not affected by the 5-HT1A receptor agonist, 8-OH-DPAT even at 100 nM. The release of glutamate evoked by 0.1 microM NAN-190 was Ca(2+)-dependent, tetrodotoxin-sensitive and inhibited significantly by 8-OH-DPAT at 1, 10 and 100 nM. These results suggest that the 5-HT1A receptor, which is located postsynaptically on glutamatergic neurons, is involved in the inhibitory regulation of glutamate release. The release of glutamate evoked by 200 microM NMDA from dentate gyrus was inhibited significantly by pretreatment with 8-OH-DPAT at 1, 10 and 100 nM. The release of glutamate evoked by 0.1 microM NAN-190 was inhibited significantly by pretreatment with MK-801 at 1 and 10 microM, a selective non-competitive NMDA receptor antagonist. The release of glutamate evoked by NMDA at 25 and 75 microM from dentate gyrus was augmented by the concurrent application of 1 nM NAN-190. We propose that the glutamate release from guinea pig dentate gyrus is regulated both by the postsynaptic 5-HT1A receptor in an inhibitory manner and by the NMDA receptor in a stimulatory manner.
Matsuyama
S
S
Department of Pharmacology, Kobe University School of Medicine, Japan.
Nei
K
K
Tanaka
C
C
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D018698:Glutamic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin