Retinoids modulate P2U purinergic receptor-mediated changes in transcervical paracellular permeability.
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 concentrations (K 1/2) = 0.1 microM] were required for restoring the phase I response than were required for reversing the phase II response (K 1/2 = 1 microM). 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.
Gorodeski
G I
GI
Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Pal
D
D
Rorke
E A
EA
Eckert
R L
RL
Burfeind
P
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002460:Cell Line; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004553:Electric Conductivity; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D010539:Permeability; D011189:Potassium Chloride / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000502:physiology*; D012176:Retinoids / Q000378:metabolism*
D003470:Culture Media; D004075:Diglycerides; D011983:Receptors, Purinergic; D012176:Retinoids; C044295:1,2-dioctanoylglycerol; D003609:Dactinomycin; D015759:Ionomycin; D011189:Potassium Chloride; D006632:Histamine; D000255:Adenosine Triphosphate