Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium.
In the present study we have compared the effects of increased intracellular Ca2+ in whole frog skin and isolated epithelium (Rana temporaria). Cellular Ca2+ was increased by the use of the endoplasmic reticulum Ca2+ ATPase inhibitor, thapsigargin. Serosal addition of thapsigargin to the whole frog skin increased the Na+ transport by increasing the apical Na+ permeability. This could be blocked by the addition of indomethacin or by removal of Ca2+ from the serosal solution. The increase in Na+ transport was accompanied by an increased prostaglandin E2 release. This indicated that the response in Na+ transport was due to a Ca2+ dependent activation of the prostaglandin E2 synthesis. Addition of thapsigargin to isolated epithelia inhibited the Na+ transport and had no effect on the prostaglandin E2 release, though the prostaglandin E2 release from the isolated epithelia could be increased by the addition of arachidonic acid. Addition of prostaglandin E2 increased the cAMP contents of the isolated epithelia significantly, whereas thapsigargin had no significant effect on the cAMP level. Our results demonstrate that serosal addition of thapsigargin causes a release of prostaglandin E2 from the dermis below the transporting epithelium. The prostaglandin E2 diffuses to the epithelium where it activates the Na+ transport by increasing cellular cAMP. The epithelium itself does not contribute significantly to the prostaglandin E2 synthesis. Furthermore an increase in intracellular Ca2+ in the epithelial cells without a concomitant increase in prostaglandin E2 release leads to an inhibition of the active Na(+)-transport.
Rytved
K A
KA
Biochemical Department, August Krogh Institute, University of Copenhagen, Denmark.
Brodin
B
B
Nielsen
R
R
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D005260:Female; D008297:Male; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors
D013729:Terpenes; D019284:Thapsigargin; D000584:Amiloride; D012964:Sodium; D015232:Dinoprostone