Effects of calcitriol on stimulation of ion transport in pig jejunal mucosa.

1. Active sodium (Na+) and chloride (Cl-) fluxes were studied in vitro in Ussing-type chambers with stripped jejunal mucosa of piglets which suffered from pseudo-vitamin D deficiency rickets, type I. The piglets are devoid of renal calcitriol (1,25-dihydroxy vitamin D3) production and have only small amounts of calbindin in their jejunal enterocytes. 2. In the presence of 0.01 mM-indomethacin non-stimulated short-circuit current (Isc), transepithelial potential difference (PD), tissue conductance (Gt) and unidirectional Na+ (JNa) and Cl- fluxes (JCl) were not affected by the low calcitriol (LC) concentration in plasma. 3. Adding 10 mM-theophylline to the serosal solution in the presence of 0.01 mM-indomethacin caused significantly greater increases in Isc in LC mucosa than in mucosa of vitamin D3-treated and control piglets with normal calcitriol (NC) concentrations in plasma. Omission of indomethacin significantly increased Isc stimulation provoked by theophylline with LC and NC mucosa. The increase, however, was significantly greater with LC than with NC mucosa. 4. Omission of calcium (Ca2+) from the serosal bathing solution significantly depressed Isc stimulation by 10 mM-theophylline in indomethacin-treated LC and NC mucosa. But depression was greater with LC than with NC mucosa. 5. Blocking Ca2+ entry into the cytosol by adding either 0.1 mM-TMB-8 or 0.5 mM-d,l-verapamil to the serosal bathing solution abolished the difference in Isc response to theophylline between indomethacin-treated LC and NC mucosa due to greater depression of Isc in LC than in NC mucosa. 6. The combined effects of theophylline and A23187 on Isc stimulation were calcitriol dependent. In the presence of indomethacin this dependence was only significant when A23187 was given prior to theophylline. In the absence of indomethacin the combined effects of A23187 and theophylline on Isc were always significantly greater in LC than in NC mucosa, irrespective of the order of adding the two agents. 7. Addition of theophylline stimulated net Na+ and Cl- secretion in indomethacin-treated LC and NC mucosa. The increases of net Na+ and Cl- fluxes fully accounted for the rise of Isc with NC mucosa but accounted only partly for the increase in Isc with LC mucosa. This resulted in significant increase in theophylline-stimulated residual ion flux (JR) in LC mucosa which probably resulted from enhanced secretion of bicarbonate.(ABSTRACT TRUNCATED AT 400 WORDS)