Effects of 1,25(OH)2D3 and calcium channel blockers on cecal calcium transport in the rat.
To determine whether calcium transport across rat cecum is vitamin D dependent, we measured in vitro bidirectional calcium fluxes under short-circuited conditions across cecum from rats that were vitamin D deficient, vitamin D replete, or vitamin D deficient or vitamin D replete and injected with either 10, 25, or 75 ng of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] daily for 4 days before study. Vitamin D deficiency decreased net calcium absorption (Jnet) by reducing the mucosal-to-serosal absorptive flux (Jm----s) from 168 +/- 18 to 33 +/- 5 nmol X cm-2 X h-1 (mean +/- SE, P less than 0.0001). Twenty-five nanograms of 1,25(OH)2D3 raised Jm----s to 124 +/- 17 nmol X cm-2 X h-1, not different from values in vitamin D-replete rats. Although active calcium absorption by cecum appears to respond to vitamin D, calcium Jm----s is near maximal under normal conditions, and further stimulation follows only pharmacological doses of 1,25(OH)2D3. The in vitro addition of the calcium channel blocker verapamil (5 X 10(-5) M) to the mucosal side of cecum from vitamin D-replete rats reduced calcium Jm----s, but lower concentrations of verapamil or nitrendipine (10(-5) to 10(-9) M) did not reduce calcium Jm----s. The lack of inhibition by low concentrations of channel blockers suggest that the plasma membrane channels for calcium translocation across intestinal epithelium may not be analogous to voltage-dependent calcium channels in excitable tissue. The inhibition of cecal calcium transport that was blocked by high concentrations of verapamil may represent a nonspecific effect of the agent.
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Angeid-Backman
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D051381:Rats; D014700:Verapamil / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism
D002121:Calcium Channel Blockers; D007473:Ion Channels; D009568:Nitrendipine; D014700:Verapamil; D002117:Calcitriol; D009543:Nifedipine; D002118:Calcium