| Abstrakt: |
In human cervical (CaSki) cells, extracellular adenosine triphosphate (ATP) induces an acute decrease in the resistance of the lateral intercellular space ( R LIS), phase I response, followed by an increase in tight junctional resistance ( R TJ), phase II response. ATP also stimulates release of calcium from intracellular stores, followed by augmented calcium influx, and both effects have similar sensitivities to ATP (EC50 of 6 μ M). The objective of the study was to determine the degree to which the changes in [Ca2+]i mediate the responses to ATP. 1,2- bis (2-aminophenoxy) ethane- N,N,N1,N1-tetraacetic acid (BAPTA) abrogated calcium mobilization and phase I response; in contrast, nifedipine and verapamil inhibited calcium influx and attenuated phase II response. Barium, La3+, and Mn2+ attenuated phase I response and attenuated and shortened the ionomycin-induced phase I-like decrease in R LIS, suggesting that store depletion-activated calcium entry was inhibited. Barium and La3+ also inhibited the ATP-induced phase II response, but Mn2+ had no effect on phase II response, and in the presence of low extracellular calcium it partly restored the increase in R TJ. KCl-induced membrane depolarization stimulated an acute decrease in R LIS and a late increase in R TJ similar to ATP, but only the latter was inhibited by nifedipine. KCl also induced a nifedipine-sensitive calcium influx, suggesting that acute increases in [Ca2+]i, regardless of mobilization or influx, mediate phase I response. Phase II-like increases in R TJ could be induced by treatment with diC8, and were not affected by nifedipine. Biphasic ATP-like changes in R TE could be induced by treating the cells with ionomycin plus diC8. We conclude that calcium mobilization mediates the early decrease in R LIS, and calcium influx via calcium channels activates protein kinase C and mediates the late increase in R TJ. [ABSTRACT FROM AUTHOR] |
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