Stimulation of [3H]norepinephrine release from hippocampal slices by excitatory amino acids.
[3H]norepinephrine efflux from preloaded rat hippocampal slices was increased in a dose-dependent manner by excitatory amino acids (EAA) in the following potency order: N-methyl-D-aspartic acid (NMDA) greater than kainic acid greater than L-glutamic acid greater than or equal to D,L-homocysteic acid greater than L-aspartic acid greater than quinolinic acid greater than quisqualic acid. The effect of EAA was blocked by physiological concentration of Mg2+, with the exception of kainic acid. D,L-2-amino-7-phosphonoheptanoic acid (APH) dose-dependently inhibited NMDA effect (IC50 = 69 mumol/L), whereas at 1 mmol/L it was ineffective versus kainic acid. The release of [3H]norepinephrine induced by quinolinic acid was blocked by APH 0.1 mmol/L. gamma-D-glutamylglycine dose-dependently inhibited kainic acid effect with an IC50 = 1.15 mmol/L. Tetrodotoxin 2 mumol/L reduced NMDA and kainic acid effects by 40 and 20%, respectively. The data indicate a possible involvement of central noradrenergic system in the modulation of excitotoxic action of EAA and offer a reliable system for testing new compounds acting at EAA-receptors by measuring norepinephrine release in vitro.
Wu
H Q
HQ
Vezzani
A
A
Samanin
R
R
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D000596:Amino Acids; D009498:Neurotoxins; D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D008274:Magnesium; C031231:2-amino-7-phosphonoheptanoic acid; D009638:Norepinephrine