[New data on the membrane mechanisms of antagonism between magnesium and alcohol: physiologic and therapeutic implications].
The aim of this study is to analyze the mechanisms involved in membrane antagonism between magnesium and ethanol. The use of both microelectrodes and metabolic inhibitors leads to distinguish 10 components of trans-amniotic conductance: 6 cellular, 1 coupling and 3 paracellular. The 6 cellular components are made up of 3 enzymatic and 3 apparently non enzymatic components. Na+K+ATPase dependent pathway, Na+H+ antiport, Na+K+2Cl- cotransport represent the 3 enzymatic components and the Na+, Cl-, K+ channels: the 3 so-called free of enzymatic mediation components. Cellular components and coupling components expressed as micromohs per "inverse" cm2 are quantitatively less important in this leaky membrane than paracellular components expressed as millimohs per "inverse" cm2. The 3 paracellular components are the Na+, Cl-, K+ pathways. On the 2 sides of aminos, the studied doses 2 mM of a Mg salt (Cl2Mg),--a concentration corresponding to the plasma level observed after therapeutic parenteral Mg load--and 0.4 g of ethanol--a concentration frequently observed in plasma after alcohol ingestion--are added to aerated Hanks' solution at 37 +/- 1 degree C and pH 7.4. Adjunction of magnesium 5 minutes before and 3 minutes after addition of ethanol permits to study the preventive and curative antagonistic effects of magnesium on ethanol action. Under these experimental conditions, magnesium significantly (p less than 0.01) increases and ethanol significantly (p less than 0.01) decreases trans-amniotic conductance. Besides magnesium significantly (p less than 0.01) induces both preventive and curative antagonistic effects on the decrease of trans amniotic conductance induced by ethanol. Moreover analysis of the 10 trans amniotic conductance components shows that both these separate effects and antagonisms are respectively neither perfectly symmetrical nor perfectly antagonistic. Magnesium significantly increases the whole group of the 10 components of trans-amniotic conductance while ethanol only decreases 7 of them. It does not exert any action on cellular Na+ and K+ channels or on the paracellular Cl- pathway. Furthermore membranous antagonistic effects between magnesium and ethanol only involve 4 components among the 7 ways affected by ethanol. They do not concern the 3 cellular enzymatic components: monovalent cation pump, Na(+)-H+ antiport, Na+K+2Cl- cotransport. As a conclusion: firstly it is not possible to extrapolate from opposite effects on conductance to antagonistic effects. Secondly an apparently perfect antagonism described from macrostudies may reveal itself imperfect when using more sophisticated microstudies. Thirdly though magnesium is a real membranous antagonist of ethanol, it cannot be described as an ideal antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)
Durlach
J
J
SDRM, Hôpital Saint-Vincent-de-Paul, Paris.
D000650:Amnion / Q000502:physiology; D004594:Electrophysiology; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D008274:Magnesium / Q000494:pharmacology* / Q000627:therapeutic use; D008564:Membrane Potentials / Q000187:drug effects
D000431:Ethanol; D008274:Magnesium
Données nouvelles sur les mécanismes membranaires d'antagonisme entre le magnésium et l'alcool: implications physiologiques et thérapeutiques.