An analysis of intestinal calcium transport across the rat intestine

Abstract

Kinetic analysis of transmural calcium transport, as evaluated by in situ intestinal loops, has confirmed the existence of two transport processes, a saturable, transcellular one that is regulated by vitamin D and predominates in the proximal intestine and a nonsaturable process similar in intensity throughout the intestine. Transport data obtained from everted sac experiments are kinetically consistent with events in the in situ loop. Analysis of the three component steps making up the saturable process, i.e., entry across the brush-border membrane, intracellular diffusion, and extrusion across the basolateral membrane, indicates that intracellular diffusion is likely to be the limiting step. Active calcium transport varies directly and proportionately with the content of calcium-binding protein (CaBP), a specific molecular expression of the action of vitamin D. Since CaBP is a cytosolic protein, it may act to facilitate calcium diffusion, a proposition advanced by Kretsinger, Mann, and Simmons and supported here quantitatively. We calculate that the rate of intracellular calcium diffusion in the absence of CaBP is only approximately 1/70 of what is found in the vitamin D-replete cell. Similar considerations have led to the proposal that calcium moved by the nonsaturable process travels largely via the paracellular route. The kinetic parameters derived here, i.e., Vm = 22 mumol X h-1 X g (wt wt-1, Km = 3.9 mM, and a nonsaturable rate of 0.16/h, can be used to predict calcium absorption data as determined in previously published balance experiments.

Vitamin D-inducible calcium transport and gene expression in three Caco-2 cell lines

“…Calcium absorption efficiency is increased by 1,25(OH) 2 D 3 . Based on a mathematical evaluation of available protein and transport data, Bronner et al (2) argued that the rate-limiting step in this process was the vitamin D-dependent production of the intracellular calcium ferry, calbindin D 9k . In addition, some studies, including our own in Caco-2 cells (32), have suggested that the cellular level of the nVDR is a critical determinant of vitamin D responses in the enterocyte.…”

“…However, while calbindin D 28k remained elevated for 32 h after its peak induction, a high rate of calcium absorption was not maintained during that same period, falling to 25% of its maximum rate. Using di-and trihomoanalogs of 1,25(OH) 2 Values are means Ϯ SE from 3 independent experiments (n ϭ 9 observations/treatment). Values within a column with different letter superscripts are significantly different from one another (Fisher's protected LSD; P Ͻ 0.05).…”

“…The active metabolite that controls this process is 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] (27). To date, two models have been proposed to explain this process: the facilitated diffusion model (2) and the vesicular model (23). In the facilitated diffusion model, summarized in Fig.…”

“…Calbindin D 9k has been proposed as the protein that binds calcium and facilitates its diffusion between the apical and basolateral surfaces of the cell (8). The level of calbindin D 9k in the intestine is closely correlated with the efficiency of calcium absorption (2), and thus this protein plays a central role in the facilitated diffusion model. In the vesicular model, the cell uses lysosomes to sequester calcium and facilitate its movement to the basolateral membrane for extrusion (24).…”

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

“…1; Hoenderop et al 2000b;Wasserman and Fullmer 1995). Active absorption of dietary Ca 2+ occurs primarily in the proximal small intestine, while in kidney active Ca 2+ reabsorption is restricted to the distal convoluted tubule (DCT) and the connecting tubule (CNT; Bronner et al 1986;Friedman and Gesek 1995).…”