RETINOIDS MODULATE P-2U PURINERGIC RECEPTOR-MEDIATED CHANGES IN TRANSCERVICAL PARACELLULAR PERMEABILITY

In human cervical cells, extracellular ATP induces an acute decrease i n the resistance of the lateral intercellular space, the phase I respo nse, followed by a delayed increase in tight junctional resistance, th e phase II response. These responses depend on vitamin A because incub ation of cells in retinoid-free medium (RFM) abolished both responses. Treatment with retinoic acid restored the phase I response in full, b ut the amplitude of the phase II response was restored only partly. Sh orter incubations and lower concentrations of retinoic acid [half-maxi mal effective concentration (K-1/2) = 0.1 mu M] were required for rest oring the phase I response than were required for reversing the phase II response (K-1/2 = 1 mu M). The phase I response could be restored b y ligands that bind to either retinoic acid receptors (RARs) or retino id X receptors, but only RAR agonists had an effect on phase II respon se. RFM had no effect on decreases in resistance induced by ionomycin, but it attenuated phase II-like increases in resistance induced by KC l or by 1,2-dioctanoyl-sn-diglycerol (diC8). Actinomycin D blocked pha se II response but not phase I response or the responses to ionomycin, KCl, or diC8. These results suggest that retinoids act on cervical ce lls via distinct retinoid receptor mechanisms and modulate phase I and phase II changes in resistance by regulating distinct signal mechanis ms.