Regulation mechanisms of intestinal Na/Ca exchanger by 1,25(OH)2D3

CENTENO V, PICOTTO G, TOLOSA DE TALAMONI N.

Rosario

Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006

Calcitriol regulates gene expression and induces rapid nontranscriptional responses in the intestine. However, intestinal Na/Ca exchanger (NCX) activity and its regulation by calcitriol remains unknown. The aim of this study was to determine calcitriol mechanisms triggered on the intestinal NCX activity. Normal controls, rachitic and rachitic chicks treated with calcitriol were used. Normal chicks fed a low calcium diet were employed in some experiments. Enterocytes were isolated and NCX activity was determined by Ca uptake experiments. The data show that NCX activity was lower in enterocytes from rachitic animals than that of normal controls. Either vitamin D treatment or low Ca diet increased the activity of the carrier. Enterocytes incubated with calcitriol also showed an increment of NCX activity. This effect was abolished by previous treatment with cycloheximide, which indicates that protein synthesis is involved in the hormone mechanism. Short exposure of the intestinal cells to calcitriol (3- 15 min) resulted in a rapid induction of the NCX activity, peaking at 5 minutes. Forskolin, adenilil cyclase activator, stimulated the NCX activity, suggesting that PKA may be a mediator in the signalling cascade that regulates the intestinal carrier activity. In conclusion, calcitriol stimulates intestinal NCX activity by genomic and non genomic mechanisms.