Biological roles of ionic zinc.
We tentatively conclude from our work that intracellular calcium acts as a second messenger to affect membrane function through activation of calmodulin. This activation, if too great, leads to pathological erythrocyte adherence and aggregation phenomena. We have shown that calmodulin inhibitors can prevent some of these calcium-induced abnormalities. Since some of this work involves a very specific anticalmodulin antibody, it appears very likely that calmodulin is involved in producing membrane effects. Zinc appears to act upon the membrane in part, at least, through the inhibition of calmodulin action. Our work leads us to believe that zinc regulates copper absorption from the gastrointestinal tract in a somewhat complex manner. That is, direct zinc-copper antagonism within the lumen of the gastrointestinal tract is not adequate to explain the effects of zinc on inhibiting copper absorption in man. It appears from our work that tissues must become loaded with zinc before an effect on copper absorption is observed. This produces a lag effect during which zinc administration does not produce a negative copper balance. However, after this lag effect, zinc has produced a negative to neutral copper balance in 5 of 5 Wilson's disease patients studied. At this time, therefore, we believe that zinc therapy can be offered as an alternative to penicillamine therapy in previously decoppered patients or patients who are not yet symptomatic. However, we recommend that this therapy only be used at this time in accordance with the one zinc therapy regimen we have tested.
D000755:Anemia, Sickle Cell / Q000188:drug therapy; D002121:Calcium Channel Blockers; D002147:Calmodulin / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects; D006527:Hepatolenticular Degeneration / Q000188:drug therapy; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D012794:Sialic Acids / Q000097:blood; D015032:Zinc / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D002147:Calmodulin; D012794:Sialic Acids; D003300:Copper; D015032:Zinc