Chronic
metabolic acidosis results in a negative
calcium balance as a result of
bone resorption and renal
calcium loss. However, reports on the changes in intestinal
calcium transport have been controversial. The present investigation therefore aimed to study the effects of chronic
metabolic acidosis induced by 1.5% NH(4)Cl administration on the three components of duodenal
calcium transport, namely,
solvent drag-induced, transcellular active, and passive paracellular components, in rats using an in vitro Ussing chamber technique. The relative
mRNA expression of genes related to duodenal
calcium transport was also determined. We found that 21-day chronic
metabolic acidosis stimulated
solvent drag-induced and transcellular active duodenal
calcium transport but not passive paracellular
calcium transport. Our results further demonstrated that an acute direct exposure to serosal acidic pH, in contrast, decreased
solvent drag-induced
calcium transport in a pH-dependent fashion but had no effect on transcellular active
calcium transport. Neither the transepithelial resistance nor duodenal permeability to Na(+), Cl(-), and Ca(2+) via the passive paracellular pathway were altered by chronic
metabolic acidosis, suggesting that widening of the tight junction and changes in the charge-selective property of the tight junction did not occur. Thus the enhanced duodenal
calcium transport observed in chronic
metabolic acidosis could have resulted from a long-term adaptation, possibly at the molecular level. RT-PCR study revealed that chronic
metabolic acidosis significantly increased the relative
mRNA expression of duodenal genes associated with
solvent drag-induced transport, i.e., the beta(1)-subunit of Na(+)-K(+)-
ATPase, zonula occludens-1,
occludin, and
claudin-3, and with transcellular active transport, i.e., transient receptor potential vanilloid family Ca(2+) channels 5 and 6 and plasma membrane Ca(2+)-
ATPase isoform 1b. Total plasma
calcium and free ionized
calcium and
magnesium concentrations were also increased, whereas serum
parathyroid hormone and
1alpha,25-dihydroxyvitamin D(3) levels were not changed. The results indicated that 21-day chronic
metabolic acidosis affected the
calcium metabolism in rats partly through enhancing the
mRNA expression of crucial duodenal genes involved in
calcium absorption, thereby stimulating
solvent drag-induced and transcellular active
calcium transport in the duodenum.