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

In human cervical cells, extracellular ATP induces an acutedecrease in the resistance of the lateral intercellular space, thephase I response, followed by adelayed increase in tight junctional resistance, thephase II response. These responses depend on vitamin A because incubation of cells in retinoid-free medium(RFM) abolished both responses. Treatment with retinoic acid restoredthe phase I response in full, but theamplitude of the phase II response wasrestored only partly. Shorter incubations and lower concentrations ofretinoic acid [half-maximal effective concentration(K_1/2) = 0.1 µM] were required for restoring the phaseI response than were required for reversing thephase II response(K_1/2 = 1 µM).The phase I response could be restoredby ligands that bind to either retinoic acid receptors (RARs) orretinoid X receptors, but only RAR agonists had an effect onphase II response. RFM had no effecton decreases in resistance induced by ionomycin, but it attenuatedphase II-like increases in resistanceinduced by KCl or by1,2-dioctanoyl-sn-diglycerol (diC8).Actinomycin D blocked phase IIresponse but not phase I response orthe responses to ionomycin, KCl, or diC8. These results suggest thatretinoids act on cervical cells via distinct retinoid receptormechanisms and modulate phase I andphase II changes in resistance byregulating distinct signal mechanisms.