Effect of vitamin D status on the rapid actions of 1,25-dihydroxycholecalciferol in rat colonic membranes.
Recent studies from our laboratory have demonstrated that the in vitro addition of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] rapidly (seconds to minutes) stimulated membrane phosphoinositide turnover, translocated protein kinase C from the cytosolic to particulate fraction, increased cytosolic calcium ([Ca2+]i), and decreased cytoplasmic pH (pHi) via inhibition of Na(+)-H+ exchange in rat colonic epithelium of dietary vitamin D-sufficient rats and in Caco-2 cells. In contrast to these prior findings, in the present experiments, 1,25(OH)2D3 failed to elicit any of these colonic biochemical responses in vitamin D-deficient animals. Bethanechol chloride also failed to alter this signal transduction pathway, [Ca2+]i, or pHi. In vivo administration of this hormone for 5-7 days, moreover, to vitamin D-deficient animals restored the rapid biochemical effects of in vitro 1,25(OH)2D3 and bethanechol chloride. These studies, therefore, indicate that alterations in the vitamin D status of rats modulate the action of 1,25(OH)2D3 and other agents on the colonic phosphoinositide signal transduction system and on [Ca2+]i, which, in turn, may influence important cellular processes in this organ such as Na(+)-H+ exchange.
Department of Medicine, Pritzker School of Medicine, University of Chicago, Illinois 60637.
R K
RK
Wali
C L
CL
Baum
M D
MD
Sitrin
M J
MJ
Bolt
P K
PK
Dudeja
T A
TA
Brasitus
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014808:Vitamin D Deficiency / Q000378:metabolism*
D001626:Bethanechol Compounds; D004075:Diglycerides; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D018723:Bethanechol; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D011493:Protein Kinase C; D002117:Calcitriol; D002118:Calcium