EFFECT OF EXTRACELLULAR ATP AND UTP ON FLUID TRANSPORT BY HUMAN NASALEPITHELIAL-CELLS IN CULTURE

We have investigated the effect of both adenosine triphosphate (ATP) a nd uridine triphosphate (UTP) on the fluid transport, transepithelial electric potential difference (PD), and unidirectional chloride flux w hen applied apically to cultured human surface respiratory epithelial (HSRE) cells in a double-compartment chamber. The effects of ATP and U TP (both 100 mu M) were examined in cells either untreated or pretreat ed with 100 mu M amiloride in lactated Ringer's solution. ATP or UTP w as added to the apical solution in a 100 mu l final volume. After a 2- h incubation period, the change in fluid transport was measured by wei ghing the apical fluid. Compared with control, amiloride blocked the f luid absorption by HSRE cells. The addition of ATP or UTP, either alon e or after pretreatment with amiloride, induced a similar and signific ant increase in the apical fluid and chloride flux (P < 0.001 and P < 0.005, respectively). The changes in both fluid transport and chloride flux were accompanied by changes in PD. A blocker for chloride transp ort, 4,4'-diisothiocyano-2,2'-stilbene disulfonate, at 500 mu M signif icantly blocked the ATP-stimulated fluid transport (P < 0.05) and chlo ride flux (P < 0.01). These results support the hypothesis that extrac ellular ATP and UTP increase the fluid transport by respiratory epithe lial cells and may be useful in the hydration of mucus and respiratory mucosa.