Evidence for involvement of protein kinase C and cyclic adenosine 3',5' monophosphate-dependent protein kinase in the 1,25-dihydroxy-vitamin D3-mediated rapid stimulation of intestinal calcium transport, (transcaltachia).
Vascularly perfused duodenal loops from normal vitamin D-replete chicks were used to obtain insight with regards to the possible mechanism(s) by which 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] rapidly stimulates intestinal Ca2+ transport (transcaltachia). The phorbol ester, 12-o-tetradecanoyl phorbol-13 acetate (TPA) (100 nM), and the adenylate cyclase activator, forskolin (10 microM), were found to stimulate Ca2+ transport from the lumen to the vascular effluent to the same extent that physiological levels of 1,25(OH)2D3 achieve. The effects of both substances exhibited concentration dependence. Similarly to 1,25(OH)2D3, addition of either TPA or forskolin to the lumenal compartment of normal chicks or vascular perfusion of duodena from vitamin D-deficient chicks failed to stimulate Ca2+ transport. Also and analogously to 1,25(OH)2-D3, TPA and forskolin-enhanced duodenal Ca2+ transport was abolished by the Ca2(+)-channel antagonists nifedipine (1 microM) and verapamil (30 microM). In addition, the protein kinase C inhibitor, staurosporine, totally abolished the rise in Ca2+ transport caused by 130 pM 1,25(OH)2D3. The synthetic peptide IP20, a well characterized cAMP-dependent protein kinase inhibitor, was also effective in suppressing 1,25(OH)2D3-dependent stimulation of duodenal Ca2+ transport. Collectively these results suggest that protein kinase C and cAMP-dependent protein kinase mediate 1,25(OH)2D3 activation of basal lateral membrane Ca2(+)-channels as an early effect in the transcaltachic response.
de Boland
A R
AR
Division of Biomedical Sciences, University of California, Riverside 92521.
Norman
A
A
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism
D000470:Alkaloids; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D014700:Verapamil; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D002117:Calcitriol; D019311:Staurosporine; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium