INTESTINAL ACTION OF VITAMIN D

Abstract

Vitamin D has a central role in the homeostasis of calcium metabolism,

regulating calcium fluxes into and out of the extracellular medium. Vitamin

D, coming from the diet or from the skin (through conversion of

7-dehydrocholesterol during exposure to ultraviolet sunrays) is transported

in plasma to the liver, where it is converted into 25(OH)-vitamin D3, which

is in turn converted in the kidney by the enzyme 1alpha-hydroxylase into

1,25(OH)2-vitamin D3 or calcitriol, the hormonally active form of the vitamin.

Calcitriol acts through a genomic mechanism mediated by an intracellular

receptor, in a way that is typical of steroid hormones, and also produces

rapid effects on calcium transport which are independent of genomic actions.

Intestinal calcium absorption is a saturable, energy-dependent process.

Calcium enters into the intestinal cell from the lumen through the brush

border membrane (BBM). Calcium-binding protein (calbindin D9 K) facilitates

calcium absorption carrying it towards the basolateral membrane (BLM), where

it is extruded to the vascular system by Ca-ATPase, the anti-porter Na+/Ca2+,

and exocytosis. The main genomic effect of calcitriol on calcium metabolism

is to increase intestinal calcium absorption, inducing the synthesis of

several proteins, including calbindin D9 K and Ca-ATPase, involved in the

cation transport. In intestinal cells the hormone activates, in a fast and

transient way, the adenylyl cyclase/AMPc/PKA and phospholipase C/IP3/DAG/PKC

intracellular messenger pathways, which participate in the regulation of

intracellular calcium promoting calcium influx through voltage-dependent

channels, and causing the release of calcium from intracellular stores. In

these cells, calcitriol also stimulates intracellular signaling pathways

leading to phosphorylation of tyrosine residues which, in turn, activate the

cytosolic tyrosin-kinase c-Src. This kinase participates in the phosphorylation

of phospholipase C-gamma and the mitogen-activated protein kinases (MAPK) ERK1

and ERK2, which regulate cellular proliferation. As a consequence of the

activation of ERK1 and ERK2, the hormone induces the expression of oncoprotein

c-Fos in intestinal cells, and stimulates DNA synthesis.