Presynaptic site of action underlying the ethanol-induced inhibition of norepinephrine release evoked by stimulation of N-methyl-D-aspartate (NMDA) receptors in rat cerebral cortex

Brain Res. 1992 Feb 14;572(1-2):27-32. doi: 10.1016/0006-8993(92)90446-g.

Abstract

Rat brain cortex synaptosomes pre-incubated with [3H]norepinephrine were used (1) to provide evidence that part of the NMDA receptors mediating stimulation of norepinephrine (NE) release are located on the noradrenergic varicosities themselves, (2) to characterize these receptors and (3) to examine whether ethanol specifically inhibits the NMDA-evoked NE release via a presynaptic site of action. In synaptosomes superfused with Mg(2+)-free Krebs-Henseleit solution, NMDA (2-min exposure) stimulated tritium overflow in a concentration- and glycine-dependent manner. The stimulatory effect of NMDA was not altered by tetrodotoxin but was abolished by omission of Ca2+ from the superfusion fluid and was considerably reduced in the presence of 1.2 mM Mg2+. DL-(E)-2-Amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849; a competitive NMDA receptor antagonist) produced a parallel shift of the concentration-response curve for NMDA to the right, whereas dizocilpine (MK-801; an antagonist at the phencyclidine, PCP, recognition site of the NMDA-gated ion channel) reduced the maximum effect of NMDA. Ethanol inhibited the NMDA-evoked tritium overflow in a concentration-dependent manner. In contrast, in synaptosomes superfused with Ca(2+)-free Krebs-Henseleit solution containing 15 mM K+ throughout, ethanol did not affect the tritium overflow evoked by 2 min introduction of 75 microM Ca2+ into the superfusion fluid. This Ca(2+)-evoked overflow was also not altered by tetrodotoxin and dizocilpine, but was inhibited by the inorganic Ca2+ channel antagonist Cd2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Cadmium / pharmacology
  • Calcium / physiology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Dizocilpine Maleate / pharmacology
  • Ethanol / pharmacology*
  • Male
  • Norepinephrine / metabolism*
  • Potassium / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Synaptosomes / physiology*
  • Tetrodotoxin / pharmacology

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Cadmium
  • 2-amino-4-methyl-5-phosphono-3-pentenoic acid
  • Ethanol
  • Tetrodotoxin
  • Dizocilpine Maleate
  • 2-Amino-5-phosphonovalerate
  • Potassium
  • Calcium
  • Norepinephrine