Ionotropic glutamate receptors regulating labeled acetylcholine release from rat striatal tissue in vitro: possible involvement of receptor modulation in magnesium sensitivity.
This study evaluated the role of glutamate ionotropic receptors on the control of [3H]acetylcholine ([3H]ACh) release by the intrinsic striatal cholinergic cells. [3H]-choline previously taken up by chopped striatal tissue and converted to [3H]ACh, was released under stimulation by glutamate, N-methyl-d-aspartate (NMDA), kainate and a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). Experiments were conducted in the absence of choline uptake inhibitors or acetylcholinesterase inhibitors. A paradigm of two stimulations was employed, the first in control conditions and the second after 9 min of perfusion with the test agents MK-801, 2-amino-5-phosphonopentanoic acid (AP-5), tetrodotoxin (TTX), 6,7-dinitroquinoxaline-2,3-dione (DNQX), 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo-[f]quinoxaline-7-sulfonamide (NBQX), glycine and magnesium. Our results support that (1) in the absence of Mg2+, NMDA is the most effective agonist to stimulate [3H]ACh release from striatal slices (2) magnesium effectively antagonized kainate and AMPA stimulation suggesting that at least part of the kainate and AMPA effects might be attributed to glutamate release (3) besides NMDA, kainate receptors showed a more direct involvement in [3H]ACh release control based on the smaller dependence on Mg2+ and less inhibition by TTX and (4) stimulation of ionotropic glutamate receptors may induce long lasting biochemical changes in receptor/ion channel function since the effects of TTX and/or Mg2+ ions on [3H]ACh release were modified by previous exposure of the tissue to agonists.
Arruda Paes
Paulo C
PC
Molecular Biology Center, Instituto de Pesquisas Energéticas e Nucleares (IPEN), Av. Prof. Lineu Prestes 2242, Cidade Universitária, SP, São Paulo 05508-900, Brazil.
de Magalhães
Leandro
L
Camillo
Maria A P
MA
Rogero
José R
JR
Troncone
Lanfranco R P
LR
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*; D014316:Tritium / Q000493:pharmacokinetics
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D014316:Tritium; D018698:Glutamic Acid; D008274:Magnesium; D002794:Choline; D000109:Acetylcholine