Rapid 1,25(OH)2-vitamin D3 stimulation of calcium uptake by rat intestinal cells involves a dihydropyridine-sensitive cAMP-dependent pathway.
The acute effects of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) on Ca2+ influx in isolated rat enterocytes were studied. The hormone significantly increased 45Ca2+ uptake by the cells within 1-10 min in a specific dose-dependent manner (10(-11)-10(-9) M) since 25(OH)D3 and 24,25(OH)2D3 were devoid of activity. The effects of 1,25(OH)2D3 were mimicked by the Ca2+ channel agonist BAY K8644 and completely abolished by nifedipine (1 microM) and verapamil (10 microM). Incubation of duodenal cells with 1,25(OH)2D3 rapidly (1-5 min) increased cAMP levels. Forskolin caused a rapid increase in Ca2+ uptake by enterocytes which was similar to the action of the hormone. Moreover, pretreatment of cells with the specific cAMP inhibitor Rp-cAMPS suppressed the changes in 45Ca influx induced by 1,25(OH)2D3. These results provide the first evidence involving Ca2+ channel activation through the cAMP pathway by 1,25(OH)2D3 in mammalian intestinal cells.
Massheimer
V
V
Departamento de Biologia, Universidad Nacional del Sur, Bahia Blanca, Argentina.
Boland
R
R
de Boland
A R
AR
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D015220:Calcium Channels; D004095:Dihydropyridines; D000242:Cyclic AMP; D002117:Calcitriol; D002118:Calcium