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

Abstract

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)