NMDA and non-NMDA ionotropic glutamate receptors modulate striatal acetylcholine release via pre- and postsynaptic mechanisms.
The effects of NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on endogenous acetylcholine release from rat striatal slices and synaptosomes were investigated. Both agonists (1-300 microM) facilitated acetylcholine release from slices in a dose-dependent manner. NMDA (100-300 microM) and AMPA (30-300 microM), however, subsequently inhibited acetylcholine release. NMDA (100 microM)-induced facilitation was antagonized by 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and dizocilpine (both 1-10 microM), whereas the 10 microM AMPA effect was antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1-30 microM). NMDA (100 microM)-induced inhibition was counteracted by CPP, but not dizocilpine, and by the nitric oxide synthase inhibitor L-nitroarginine (1-100 microM). Tetrodotoxin (0.5 microM) prevented the facilitatory effect of 3 microM NMDA and AMPA, but left unchanged that of 30 microM NMDA and 100 microM AMPA. Acetylcholine release from synaptosomes was stimulated by KCl (7.5-100 mM) in a dose-dependent manner. NMDA and AMPA maximally potentiated the 20 mM KCl effect at 1 microM and 0.01 microM, but were ineffective at 100 microM and 10 microM, respectively. Inhibition of acetylcholine release was never found in synaptosomes. The effects of 1 microM NMDA and 0.01 microM AMPA were antagonized by CPP (0.0001-1 microM) or dizocilpine (0.0001-10 microM) and by CNQX (0.001-1 microM), respectively. These data suggest that glutamatergic control of striatal acetylcholine release is mediated via both pre- and postsynaptic NMDA and non-NMDA ionotropic receptors.
Morari
M
M
Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
Sbrenna
S
S
Marti
M
M
Caliari
F
F
Bianchi
C
C
Beani
L
L
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D011189:Potassium Chloride; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000109:Acetylcholine; D002118:Calcium