title: 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 (PAMan) and in alveolar liquid absorption (Jw, twofold) in isolated rat lungs. These increases were inhibited by 5 x 10(-3) mol/l putrescine and 2 x 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 Jw. 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 Jw. They also suggest that the phosphoinositide/Ca2+ second messenger pathway is involved in modulating the tightness of the alveolar barrier and alveolar liquid absorption.
authors.affiliation: INSERM U82, Faculté Xavier Bichat, Paris, France. saumon@bichat.inserm.fr
authors.forename: G
authors.initials: G
authors.lastname: Saumon
authors.forename: G
authors.initials: G
authors.lastname: Martet
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D005033:Ethylmaleimide / Q000494:pharmacology; D007202:Indicators and Reagents; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating / Q000187:drug effects; D008353:Mannitol / Q000378:metabolism; D008634:Mersalyl / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013849:Thimerosal / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007202:Indicators and Reagents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010716:Phosphatidylinositols; D018160:Receptors, Cytoplasmic and Nuclear; D013438:Sulfhydryl Compounds; D013849:Thimerosal; D013096:Spermine; D008353:Mannitol; D008634:Mersalyl; D000584:Amiloride; D015544:Inositol 1,4,5-Trisphosphate; D005033:Ethylmaleimide; D002118:Calcium; D013095:Spermidine; D011700:Putrescine