Regulation of the paracellular permeability of cultured human cervical epithelium by a nucleotide receptor.
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 pyranine (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 omega/cm2 and a decrease in Ppyr 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 microM), saturable at 50 microM, and desensitized with repeated administration; it was mimicked by uridine triphosphate and ATP-gamma-S but not by adenosine monophosphate, adenine, 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.
Gorodeski
G I
GI
Department of Reproductive Biology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
Hopfer
U
U
D000225:Adenine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D014544:Uridine Triphosphate / Q000494:pharmacology
D018048:Receptors, Purinergic P2; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000225:Adenine; D000241:Adenosine; D014544:Uridine Triphosphate