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Am J Physiol Cell Physiol 274: C1108-C1116, 1998;
0363-6143/98 $5.00
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Vol. 274, Issue 4, C1108-C1116, April 1998

Retinoids modulate P2U purinergic receptor-mediated changes in transcervical paracellular permeability

George I. Gorodeski1,2, Dipika Pal1, Ellen A. Rorke3, Richard L. Eckert2, and Peter Burfeind1

Departments of 1 Reproductive Biology, 2 Physiology and Biophysics and 3 Environmental Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

In human cervical cells, extracellular ATP induces an acute decrease in the resistance of the lateral intercellular space, the phase I response, followed by a delayed increase in tight junctional resistance, the phase II response. These responses depend on vitamin A because incubation of cells in retinoid-free medium (RFM) abolished both responses. Treatment with retinoic acid restored the phase I response in full, but the amplitude of the phase II response was restored only partly. Shorter incubations and lower concentrations of retinoic acid [half-maximal effective concentration (K1/2) = 0.1 µM] were required for restoring the phase I response than were required for reversing the phase II response (K1/2 = 1 µM). The phase I response could be restored by ligands that bind to either retinoic acid receptors (RARs) or retinoid X receptors, but only RAR agonists had an effect on phase II response. RFM had no effect on decreases in resistance induced by ionomycin, but it attenuated phase II-like increases in resistance induced by KCl or by 1,2-dioctanoyl-sn-diglycerol (diC8). Actinomycin D blocked phase II response but not phase I response or the responses to ionomycin, KCl, or diC8. These results suggest that retinoids act on cervical cells via distinct retinoid receptor mechanisms and modulate phase I and phase II changes in resistance by regulating distinct signal mechanisms.

human; cervical cells; extracellular ATP; tight junctions; vitamin A; lateral intercellular space; transepithelial transport; cervical mucus


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