P. Nybom et Ke. Magnusson, STUDIES WITH WORTMANNIN AND CYTOCHALASINS SUGGEST A PIVOTAL ROLE OF PHOSPHATIDYLINOSITOLS IN THE REGULATION OF TIGHT JUNCTION INTEGRITY, Bioscience reports, 16(3), 1996, pp. 265-272
Wortmannin, a selective inhibitor of phosphatidylinositol 3-kinase (P1
3K), was found to give a dose and time-dependent, bimodal effect-initi
al increase, followed by decrease on the tight junction integrity of M
DCK-1 monolayers, as assessed by electrical resistance measurement of
the epithelia. Moreover, dihydrocytochalasin B inhibited the wortmanni
n-induced alteration, whereas cytochalasin B had a negligible influenc
e on the wortmannin effect. Wortmannin was also found to cause changes
in the cytoskeleton structure. These alterations were also seen when
wortmannin was combined with cytochalasin B. However, in accordance wi
th the electrical resistance measurements, dihydrocytochalasin B was a
ble to abolish wortmannin-induced filamentous (F-) actin changes. Thes
e findings suggest that the P13K, phosphatidylinositols, and filamento
us actin rearrangements, in combination, play an important role in the
modulation of the junctional integrity.