Effects of various metals on hepatic bile calcium excretion in rats: the stimulatory effect of zinc is mediated through acetylcholine action.
The effect of various metals on hepatic bile calcium excretion in rats was investigated. Various metals (0.153 mumol per 100 g body weight) were administered intraperitoneally to rats after cannulation of the bile duct, and the bile was collected for 30 min. Bile calcium excretion was significantly increased by administration of zinc sulfate, cadmium chloride, cobalt chloride, lithium chloride, manganese chloride, and nickel chloride, while it was not altered by strontium chloride and cupric sulfate. Of these metals, the effect of zinc was most remarkable. An appreciable effect of zinc on bile calcium excretion was seen at 7.65 nmol (0.5 micrograms) Zn/100 g, the lowest dose. The stimulatory effect of zinc on bile calcium excretion was completely blocked by the simultaneous administration of verapamil and diltiazem (1.0 mg/100 g), calcium entry blockers, whereas the effects of cadmium and manganese were not prevented by the drugs. Also, the effect of zinc on increasing bile calcium excretion was completely inhibited by treatment with atropine (10 micrograms/100 g). Furthermore, administration of acetylcholine (2 and 5 micrograms/100 g) produced a remarkable elevation of bile calcium excretion. The present investigation demonstrates that zinc can stimulate bile calcium excretion in rats and that the effect may be mediated through acetylcholine action.
Yamaguchi
M
M
Department of Environmental Biochemistry and Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Uematsu
T
T
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001646:Bile / Q000032:analysis*; D002118:Calcium / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
D001285:Atropine; D014700:Verapamil; D004110:Diltiazem; D015032:Zinc; D000109:Acetylcholine; D002118:Calcium