Wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits transcytosis in polarized epithelial cells.

Wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits both basolateral to apical and apical to basolateral transcytosis of ricin in Fisher rat thyroid (FRT) cells by 50% at 100 nM in a continuous transcytosis assay. In MDCK cells, a similar effect of wortmannin on basolateral to apical transcytosis of ricin was found, whereas apical to basolateral transcytosis was inhibited to a lesser degree. Transcytosis of dimeric IgA in MDCK cells expressing the polymeric immunoglobulin receptor was also reduced to 50% of controls, suggesting that wortmannin inhibits membrane translocation rather than sorting of specific proteins in the transcytotic pathway. This effect of wortmannin is selective, however, in that endocytosis at the basolateral domain and recycling at both the basolateral and apical membrane domains are unaffected, and apical endocytosis and apical secretion are only moderately reduced. We have shown previously that cAMP stimulates a late stage in basolateral to apical transcytosis in MDCK cells through activation of protein kinase A (Hansen, S. H., and Casanova, J.E. (1994) J. Cell Biol. 126, 677-687). Elevation of cellular cAMP still induced a 100% increase in transcytosis in wortmannin-treated cells, but transcytosis was no longer increased when compared to cells which received no drugs. In contrast, in experiments using a 17 degrees C block to accumulate ricin internalized from the basolateral surface in the apical compartment of MDCK cells, wortmannin had little effect on the stimulation of transcytosis by activators of protein kinase A observed under these conditions. The data thus suggest the existence of a wortmannin-sensitive step in the transcytotic pathway, positioned after endocytosis but prior to translocation into the protein kinase A-sensitive apical compartment, implying a role for phosphoinositide 3-kinase in an intermediate step in transcytosis in polarized epithelial cells.

[Iodine metabolism in leprosy patients (study using a whole-body radiometry method)]. / Iodnyi obmen u bol'nykh leproi (issledovanie metodom radiometrii vsego tela).

A method of total body radiometry was used to study iodine metabolism in 47 patients with lepromatous leprosy. Disorders were found in 1/3 of the cases. The level of organic iodine in the body was the most informative of all iodine metabolism indices. In the active stage of leprosy it was twice as low, on an average, as the normal one, in the stage of incomplete and stable regression it rose not reaching, however, the values of healthy persons. The lowest mean value of an organic iodine level in the body was observed in patients with noticeable specific polyneuritis. The content of iodine in the thyroid of leprosy patients showed a tendency to a rise starting from the active stage, however it was only in the stages of incomplete and stable regression that it significantly exceeded the normal level. The data obtained should be considered during therapy of lepers to predict and control an unfavorable complication like specific polyneuritis.