Met-enkephalin release from slices of the rat striatum and globus pallidus: stimulation by excitatory amino acids.
The present study evaluated the effects of high K+ and four excitatory amino acids (EAAs) on the release of met-enkephalin-like immunoreactivity (ME-i.r.) from slices of the rat striatum and globus pallidus. High K+ (15-50 mM) increased the release of ME-i.r. in a concentration-dependent manner in both regions, the release response in the globus pallidus being consistently greater than in the striatum. This release was highly Ca(++)-dependent and was significantly enhanced in the absence of external Mg++. D-2-Amino-7-phosphonoheptanoic acid (0.5 mM), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter this enhanced action of K+, suggesting that the activation of NMDA receptors by an endogenous agonist did not contribute to the enhancement. Exposure of pallidal or striatal slices to four EAA receptor agonists, NMDA, L-glutamate, kainate (KA) and quisqualate, increased the release of ME-i.r. above the base line, an effect that was Ca(++)-dependent. Both L-glutamate and NMDA, at concentrations of 1 and 5 mM, produced a graded increase in the ME-i.r. release, but a higher concentration (10 mM) produced a lower release. In both regions the NMDA (5 mM)-evoked release was effectively inhibited by Mg++ (1.2 mM), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (5 microM), a competitive NMDA receptor antagonist and thienylcyclohexylpiperidine (10 microM), a noncompetitive NMDA receptor antagonist. Tetrodotoxin (0.3 microM), a Na+ channel blocker, did not affect the NMDA-evoked release of ME-i.r. in the striatum, but decreased it by 52% in the globus pallidus.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada.
B B
BB
Ruzicka
K
K
Jhamandas
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D000596:Amino Acids; D005971:Glutamates; D018698:Glutamic Acid; D004744:Enkephalin, Methionine; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D011188:Potassium; D007608:Kainic Acid