Spermine increases the active and passive transport across the alveolar epithelium in situ: effect of thiol reagents

Abstract.

An intact alveolar epithelial barrier is thought to be important for alveolar liquid absorption. However, polycations increase alveolar permeability without affecting alveolar liquid absorption (Saumon et al., Am J Physiol 1995; 269:L185–L194). We have reconsidered this issue using polyamines. The polyamine spermine (10^–3 mol/l) produced a large (up to 20-fold), sustained increase in the permeability of the alveolar barrier to mannitol (PA_Man) and in alveolar liquid absorption (J _w, twofold) in isolated rat lungs. These increases were inhibited by 5·10^–3 mol/l putrescine and 2·10^–3 mol/l spermidine. Because spermine is known to affect the phosphoinositide/Ca²⁺ signalling pathway, we evaluated the effects of thiol reagents known to interfere with this pathway in different ways. Thimerosal, a thiol reagent which sensitizes the inositol 1,4,5-trisphosphate (IP₃) receptor, inhibited the spermine-induced increase in PA_Man and, to a lesser extent, that of J _w. Mersalyl, a thiol reagent which blocks IP₃-gated Ca²⁺ channels, enhanced spermine's effect, whereas N-ethylmaleimide, a non-specific thiol reagent, had no effect. These observations show that large increases in permeability may coexist with increases in J _w. They also suggest that the phosphoinositide/Ca²⁺ second messenger pathway is involved in modulating the tightness of the alveolar barrier and alveolar liquid absorption.