Inhibition of N-methyl-D-aspartate (NMDA)- and L-glutamate-induced noradrenaline and acetylcholine release in the rat brain by ethanol

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 340; no. 5; pp. 516 - 521
• Main Authors: GÖTHERT, M, FINK, K
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-11-1989; Berlin; New York, NY
• Subjects: Acetylcholine - metabolism; Alcoholism and acute alcohol poisoning; Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Biological and medical sciences; Calcium - physiology; Cerebral Cortex - enzymology; Choline - metabolism; Corpus Striatum - metabolism; Ethanol - pharmacology; Glutamates - pharmacology; Glutamic Acid; Magnesium - pharmacology; Male; Medical sciences; N-Methylaspartate; Norepinephrine - metabolism; Rats; Rats, Inbred Strains; Toxicology; Tritium; Veratridine - pharmacology; Glutamic acid; Cerebral cortex; Ethanol; Rat; Toxicity; Rodentia; Central nervous system; Corpus striatum; In vitro; Vertebrata; Mammalia; Animal; Excitatory aminoacid; Acetylcholine; Norepinephrine; Mechanism of action; Release; Biological receptor
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00260606

The influence of ethanol on stimulation-evoked 3H-transmitter release was examined in slices of the rat brain cortex and corpus striatum preincubated with 3H-noradrenaline and 3H-choline, respectively. 3H-Transmitter release was stimulated by NMDA, L-glutamate, electrical impulses, reintroduction of Ca2+ ions ("Ca2(+)-evoked release", after superfusion with Ca2(+)-free, K(+)-rich solution) or veratridine. In cortical slices preincubated with 3H-noradrenaline and superfused with Mg2(+)-free, otherwise physiologically composed salt solution, ethanol inhibited the NMDA- or L-glutamate-induced tritium overflow (IC50 45 and 37 mmol/l, respectively). In contrast, the tritium overflow in response to electrical stimulation, reintroduction of Ca2+ ions or veratridine was not affected by ethanol at concentrations up to 320 mmol/l; these experiments were carried out in cortical slices superfused with solution containing a physiological Mg2+ concentration. Ethanol also failed to inhibit Ca2(+)-evoked release in the absence of Mg2+ ions. In the presence of 1 mumol/l veratridine, but not in its absence, NMDA induced tritium overflow even when cortical slices were superfused with salt solution containing a physiological Mg2+ concentration; again, ethanol inhibited this NMDA-evoked tritium overflow (IC50 73 mmol/l. In striatal slices preincubated with 3H-choline and superfused with Mg2(+)-free "physiological" salt solution the NMDA-evoked tritium overflow was also, although at lower potency, inhibited by ethanol (IC50 192 mmol/l). In spite of the differences between the IC50 values of ethanol determined for the inhibition of cortical noradrenaline and striatal acetylcholine release, it may be concluded that the NMDA receptor-ion channel complex is one of the sites of action underlying the ethanol-induced inhibition of neurotransmitter release.