Theophylline affects active and passive electrolyte transport in in vitro rabbit ileum

Theophylline, 10 mM, in the serosal bathing solution of short circuited rabbit ileum, caused a reversal of net transport from absorption to secretion of both Na (1.0±0.1 to -0.6±0.1 μEq/hr cm²) and Cl (0.7±0.3 to -1.8±0.2), and lowered both unidirectional fluxes of these ions. Short circuit current was increased transiently, but there was a sustained increase in potential difference (P.D.), and tissue conductance was reduced by 50%. Ouabain, 10^-4 M, abolished net Na and Cl transport in both control and treated tissues, but current voltage curves showed that the theophylline induced conductance change was still present (24.0±0.2 to 15.5±0.1 mmho/cm²). From P.D. changes resulting from the serial dilution of mucosal solution NaCl with mannitol or KCl in paired, ouabain treated, control and theophylline tissues, the relative permeabilities of Na, K, and Cl were calculated. In controls pK:pNa:pCl was 1.18:1.00:0.47 and in theophylline 1.15:1.00:0.68. It was concluded that theophylline has two major effects in the in vitro rabbit ileum: It stimulates the active secretion of Na and Cl, perhaps through a coupled mechanism, and it reduces the magnitude and changes the permselective characteristics of the transepithelial shunt path.