Simultaneous action of MK-801 (dizclopine) on dopamine, glutamate, aspartate and GABA release from striatum isolated nerve endings.
The simultaneous effect of MK-801 on the baseline- and depolarization (20 microM veratridine or 30 mM high K+)-evoked release of endogenous dopamine, glutamate (Glu), aspartate (Asp), and GABA is investigated in the same preparation of rat striatum isolated nerve endings. MK-801, in the microM range, selectively increases the baseline and high K+ depolarization-evoked release of dopamine, without causing any effect on the baseline or on the high K+-evoked release of Glu, Asp and GABA. In addition to this selective action on dopamine release, MK-801 inhibits the veratridine depolarization-evoked release of all the neurotransmitters tested, including dopamine. In SBFI and fura-2 preloaded striatal synaptosomes, MK-801 inhibits the elevation of internal Na+ (Na(i)) and the elevation of internal Ca2+ (Ca(i)) induced by veratridine depolarization. The elevation of Ca(i) induced by high K+ depolarization is unchanged by MK-801. This study reveals two separate MK-801 actions. (1) The voltage-independent action, which increases dopamine release selectively, and might contribute to the effects of MK-801 on motor coordination. (2) The voltage-dependent action, which inhibits all the veratridine-evoked responses including the evoked release of the excitatory amino acids (which are particularly concentrated in striatum nerve endings), and might contribute to the anticonvulsant and neuroprotective effects of MK-801.
Sitges
M
M
Depto. de Biología Celular, Instituto de Investigaciones Biomédicas, UNAM, México, DF, México. sitges@servidor.unam.mx
Nekrassov
V
V
Guarneros
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D005973:Glutamine; D015102:3,4-Dihydroxyphenylacetic Acid; D016291:Dizocilpine Maleate; D014701:Veratridine; D011188:Potassium; D002118:Calcium