Chronic metabolic acidosis resulted in negative calcium balance as a result of bone resorption and renal calcium loss.However, reports on the changes in the intestinal calcium transport were controversial.The present investigation therefore aimed to study the effects of chronic metabolic acidosis induced by 1.5%NH₄Cl administration on the three components of the duodenal calcium transport,namely solvent drag-induced,transcellular active and passive paracellular components in rats by using an in vitro Ussing chamber technique.Relative mRNA expression of genes related to the duodenal calcium transport was also determined.We found that 21-day chronic metabolic acidosis stimulated the solvent drag-induced and transcellular active duodenal calcium transport,but not the passive paracellular calcium transport.Our results further demonstrated that an acute direct exposure to serosal acidic pH,in contrast,decreased the solvent drag-induced calcium transport in a pH-dependent fashion,but had no effect on the transcellular active calcium transport.Neither the transepithelial resistance nor duodenal permeability to Na⁺,Cl^-,and Ca²⁺ 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 the solvent drag-induced transport,i.e.1-subunit of Na⁺/K⁺-ATPase,ZO-1,occludin and claudin-3,and with the transcellular active transport,i.e.TRPV5,TRPV6,and PMCA1b.Total plasma calcium,free-ionized calcium and magnesium concentrations were also increased,whereas serum parathyroid hormone and 1,25-(OH)₂D₃ levels were not changed. (Truncated)