Objective:We sought to determine what type of regulation of transepithelial transport in leaky epithelium can occur at the level of paracellular permeability.
Methods:The epithelial permeability to the polar acid pyramine (Ppyr) and the transepithelial electrical resistance (R) were determined in cultured human cervical epithelium.
Results:Extracellular adenosine triphosphate (ATP) acutely and reversibly decreased the paracellular permeability, as evidenced by an increase of R from 10 ± 3 to 16 ± 2 μ/cm2 and a decrease in Ppyr from 13 ± 3 to 9 ± 3 × 10-6 cm/sec and (P < .01 for both). The ATP effect was dose related (average median effective concentration 2 ± 1 μM), saturable at 50 μM, and desensitized with repeated administration; it was mimicked by uridine triphosphate and ATP-γ-S but not by adenosine monophosphate, ademine, adenosine, or adenosine diphosphate. The ATP effect on resistance remained intact even when the intercellular resistance was decreased with a basal-to-apical pressure gradient, but was abolished by lowering extracellular calcium.
Conclusions:These results indicate the following: 1) Paracellular permeability in the cervical 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 the cervix in vivo by acting on a surface receptor and by increasing the resistance of the tight junctions.
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