BIPHASIC REGULATION OF PARACELLULAR PERMEABILITY IN HUMAN CERVICAL CELLS BY 2 DISTINCT NUCLEOTIDE RECEPTORS

The effects of extracellular ATP (ATP(e)) were characterized in human cervical cells grown on filters. ATP(e) changed the transepithelial conductance (G(T)) in a biphasic manner with an initial acute increase of 13 +/- 3% (phase I), lasting similar to 2 min, followed by a sustained decrease of 49 +/- 17% (phase II). ATP(e) also effected decreases of permeabilities to pyranine and to sucrose, which correspond to the phase II decrease in G(T). Both phase I and II effects appear to be mediated by apical nucleotide receptors. However, the phase I effect differed from the phase II effect as follows: 1) a higher 50% effective concentration for ATP(e), 22 vs. 3 mu M; 2) different nucleotide specificity; 3) lack of influence of pretreatment with pertussis toxin; 4) independence from time in culture after seeding; and 5) involvement of cytosolic calcium, rather than diacylglycerol, as intracellular messenger. These differences suggest the presence of two different types of nucleotide receptors that use different intracellular signaling systems and have opposite effects on the paracellular permeability and electrical conductance. These results suggest that ATP(e) could regulate cervical mucus production in vivo by regulating the paracellular permeability. Depending on the specific receptors present, ATP(e) could either increase or decrease mucus production.