PROSTAGLANDIN E(2) RELEASE FROM DERMIS REGULATES SODIUM PERMEABILITY OF FROG-SKIN EPITHELIUM

In the present study we have compared the effects of increased intrace llular Ca2+ in whole frog skin and isolated epithelium (Rana temporari a). Cellular Ca2+ was increased by the use of the endoplasmic reticulu m Ca2+ ATPase inhibitor, thapsigargin. Serosal addition of thapsigargi n to the whole frog skin increased the Na+ transport by increasing the apical Na+ permeability. This could be blocked by the addition of ind omethacin or by removal of Ca2+ from the serosal solution. The increas e in Na+ transport was accompanied by an increased prostaglandin E(2), release. This indicated that the response in Na+ transport was due to a Ca2+ dependent activation of the prostaglandin E(2) synthesis. Addi tion of thapsigargin to isolated epithelia inhibited the Na+ transport and had no effect on the prostaglandin E(2) release, though the prost aglandin E(2) release from the isolated epithelia could be increased b y the addition of arachidonic acid. Addition of prostaglandin E(2) inc reased the cAMP contents of the isolated epithelia significantly, wher eas thapsigargin had no significant effect on the cAMP level. Our resu lts demonstrate that serosal addition of thapsigargin causes a release of prostaglandin E(2) from the dermis below the transporting epitheli um. The prostaglandin E(2) diffuses to the epithelium where it activat es the Na+ transport by increasing cellular cAMP. The epithelium itsel f does not contribute significantly to the prostaglandin E(2) synthesi s. Furthermore an increase in intracellular Ca2+ in the epithelial cel ls without a concomitant increase in prostaglandin E(2) release leads to an inhibition of the active Na+-transport.