Effect of treatment time on calcium antagonism by cadmium ions in a guinea-pig taenia coli.
1. When pretreated for 1 min, with Cd2+ at low concentrations (0.001-0.01 mM), there was a parallel rightward shift of Ca2+ concentration-curves in guinea-pig taenia coli in K+-depolarized Ca2+-free medium. However, when pretreated for 30 min, Cd2+ reduced the maximal Ca2+ response size. 2. The application of 0.01 mM Cd2+ for 1, 5 and 30 min in Ca2+-free, K+-medium reduced to the same degree the Ca uptake after addition of 3 mM Ca2+. The inhibitory action on the tension by Cd2+ however, became greater as the pretreatment time with Cd2+ increased. 3. Within 5 min of Cd2+ (0.01 mM) treatment, Cd2+ chiefly bound to the cell membrane, however, with a longer duration (30 min), Cd2+ entered the cytoplasm where EDTA could not reach. 4. Cd2+ above 0.0005 mM reduced dose-dependently the respiration of isolated mitochondria. 5. These results suggest that with short duration exposure (1-5 min) of taenia coli cells to Cd2+, the interference with Ca2+ entry through voltage-dependent Ca2+ channels is predominant but for longer exposure times, intracellular actions of Cd2+ contribute to its inhibitory effects.
Nasu
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Department of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University, Japan.
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors*; D002462:Cell Membrane / Q000378:metabolism; D003106:Colon / Q000187:drug effects*; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004492:Edetic Acid / Q000493:pharmacokinetics; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D011485:Protein Binding; D013997:Time Factors
D002104:Cadmium; D004492:Edetic Acid; D002118:Calcium