REGULATION OF THE PARACELLULAR PERMEABILITY OF CULTURED HUMAN CERVICAL EPITHELIUM BY A NUCLEOTIDE RECEPTOR

OBJECTIVE: We sought to determine what type of regulation of transepit helial transport in leaky epithelium can occur at the level of paracel lular permeability. METHODS: The epithelial permeability to the polar acid pyranine (P-pyr and the transepithelial electrical resistance (R) were determined in cultured human cervical epithelium. RESULTS: Extra cellular adenosine triphosphate (ATP) acutely and reversibly decreased the paracellular permeability, as evidenced by an increase of R from 10 +/- 3 to 16 +/- 2 Omega/cm(2) and a decrease in P-pyr from 13 +/- 3 to 9 +/- 3 x 10(-6) cm/sec and (P < .01 for both). The ATP effect was dose related (average median effective concentration 2 +/- 1 mu M), s aturable at 50 mu M, and desensitized with repeated administration; it was mimicked by uridine triphosphate and ATP-gamma-S but nor by adeno sine monophosphate, adenine, adenosine, or adenosine diphosphate. The ATP effect on resistance remained intact even when the intercellular r esistance was decreased with a basal-to-apical pressure gradient, but was abolished by lowering extracellular calcium. CONCLUSIONS: These re sults indicate the following: 1) Paracellular permeability in the cerv ical epithelial cell line is regulated by a nucleotide receptor; and 2 ) the tight junctions are effectors of nucleotide-receptor stimulation . We suggest that extracellular ATP may regulate mucus production in t he cervix in vivo by acting on a surface receptor and by increasing th e resistance of the tight junctions.