N-methyl-D-aspartate (NMDA) receptor-mediated stimulation of noradrenaline release, but not release of other neurotransmitters, in the rat brain cortex: receptor location, characterization and desensitization.
Rat brain cortex slices and synaptosomes (in a few experiments also hippocampal synaptosomes) preincubated with 3H-noradrenaline, 3H-5-hydroxytryptamine, 3H-choline, 3H-glutamate or 3H-gamma-aminobutyric acid were used to investigate the 3H-transmitter release in response to exposure to N-methyl-D-aspartate (NMDA) and other excitatory amino acids. The slices and synaptosomes were superfused with Mg2+-free, otherwise physiologically composed salt solution. In cortical slices preincubated with 3H-noradrenaline, NMDA concentration-dependently stimulated 3H overflow, whereas no such effect occurred in slices preincubated with 3H-5-hydroxytryptamine, 3H-choline, 3H-glutamate or 3H-gamma-aminobutyric acid. In cortical slices preincubated with 3H-noradrenaline, the NMDA-evoked 3H overflow was abolished by tetrodotoxin, presence of Mg2+ 1.2 mmol/l or absence of Ca2+. 2-Amino-5-phosphonovaleric acid produced a parallel shift to the right of the NMDA concentration-response curve, whereas (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept- 5,10-imine hydrogen maleate (MK-801) not only shifted the concentration-response curve to the right but also reduced the maximum effect of NMDA. Other excitatory amino acid receptor agonists also stimulated 3H overflow, yielding the following rank order of potency: NMDA greater than L-glutamate greater than L-aspartate. Kainate and, in particular, quisqualate exhibited only low potencies and/or intrinsic activities. Prolonged (25 min) exposure of 3H-NA-preincubated cortical slices to a high NMDA concentration produced a short-lasting peak of 3H overflow, followed by a second phase lasting as long as the compound was present; in this phase, 3H overflow was clearly less pronounced and gradually decreased with time.(ABSTRACT TRUNCATED AT 250 WORDS)
Fink
K
K
Institut für Pharmakologie und Toxikologie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Federal Republic of Germany.
Göthert
M
M
Molderings
G
G
Schlicker
E
E
D015763:2-Amino-5-phosphonovalerate; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D005971:Glutamates; D018377:Neurotransmitter Agents; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; D006916:5-Hydroxytryptophan; D014633:Valine; D002794:Choline; D009638:Norepinephrine