Biphasic regulation of paracellular permeability in human cervical cells by two distinct nucleotide receptors.
The effects of extracellular ATP (ATPe) were characterized in human cervical cells grown on filters. ATPe changed the transepithelial conductance (GT) in a biphasic manner with an initial acute increase of 13 +/- 3% (phase I), lasting approximately 2 min, followed by a sustained decrease of 49 +/- 17% (phase II). ATPe also effected decreases of permeabilities to pyranine and to sucrose, which correspond to the phase II decrease in GT. Both phase I and II effects appear to be mediated by apical nucleotide receptors. However, the phase I effect differed from the phase II effect as follows: 1) a higher 50% effective concentration for ATPe, 22 vs. 3 microM; 2) different nucleotide specificity; 3) lack of influence of pretreatment with pertussis toxin; 4) independence from time in culture after seeding; and 5) involvement of cytosolic calcium, rather than diacylglycerol, as intracellular messenger. These differences suggest the presence of two different types of nucleotide receptors that use different intracellular signaling systems and have opposite effects on the paracellular permeability and electrical conductance. These results suggest that ATPe could regulate cervical mucus production in vivo by regulating the paracellular permeability. Depending on the specific receptors present, ATPe could either increase or decrease mucus production.
Gorodeski
G I
GI
Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Hopfer
U
U
De Santis
B J
BJ
Eckert
R L
RL
Rorke
E A
EA
Utian
W H
WH
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002460:Cell Line; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D009994:Osmolar Concentration; D010539:Permeability / Q000187:drug effects; D037342:Pertussis Toxin; D011956:Receptors, Cell Surface / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004075:Diglycerides; D009711:Nucleotides; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; C044295:1,2-dioctanoylglycerol; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D008274:Magnesium