Trifluoperazine stimulated sodium transport by increased prostaglandin E2 synthesis in isolated frog skin (Rana esculenta).
Addition of trifluoperazine (TFP) to the inside bathing solution of the isolated frog skin resulted in a biphasic increase in the short-circuit current (SCC). The Na+-flux measurements showed that the TFP-induced increase of SCC was accounted for by active sodium transport. The intracellular voltage in short circuited skins changed after addition of TFP (100 microM) from a control value of -80.9 +/- 0.8 to -66.2 +/- 1.0 mV (n = 8). This depolarization indicates that TFP acts by increasing the Na+-permeability of the apical membrane. The biphasic increase in SCC is due to different mechanisms. The primary activation could be abolished by the calcium ionophore A23187, whereas the secondary activation could be abolished by the prostaglandin synthesis inhibitor indomethacin, PGE2 or A23187. Stimulation of the SCC by TFP and theophylline or antidiuretic hormone (AVT) was additive. Furthermore, TFP did not increase the cAMP level of isolated epithelia or theophylline-stimulated epithelia. These results indicate that the TFP-induced change in the Na+-permeability was not due to an enhanced cAMP level. The TFP simulated SCC requires Ca2+ in the inside bathing solution. Addition of TFP resulted in an increase in prostaglandin E2 release to the inside bathing solution from a control value of 0.31 +/- 0.04 to 5.4 +/- 1.4 pmol PGE2 h-1 cm-2 (n = 8). It is suggested that TFP induces a Ca2+-dependent PGE2 synthesis, leading to an increase in the intracellular PGE2 concentration which might increase the Na+-permeability of the apical membrane.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011458:Prostaglandins E / Q000096:biosynthesis*; D011893:Rana esculenta; D012867:Skin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology
D011458:Prostaglandins E; D014667:Vasopressins; D014268:Trifluoperazine; D000001:Calcimycin; D012964:Sodium; D013806:Theophylline; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin