Cyclosporin A stimulates Na+ transport across the isolated skin of Rana esculenta.
Cyclosporin A (Cs A), added to the fluid bathing the internal surface of the isolated skin of Rana esculenta, increased short-circuit current (SCC) with a maximal effect at 5 microM. This effect was completely inhibited by amiloride (0.2 mM in the fluid bathing the external surface). By measuring both transepithelial fluxes of 22Na+ across symmetrical parts of the short circuited skin, Cs A was found to increase the net absorption of Na+. Naproxen (10 microM), a cyclooxygenase inhibitor, decreased the stimulation by Cs A of SCC, suggesting that in this stimulation prostaglandins are involved. The Cs A effect on Na+ transport could be caused by an inhibition of a Ca2+/calmodulin-dependent protein phosphatase, i.e. calcineurin, since: a) it is mimicked by another inhibitor of calcineurin, i.e. fenvalerate: b) the action of Cs A and fenvalerate on SCC are decreased by the calmodulin inhibitor W7.
Lippe
C
C
Istituto di Fisiologia Generale, Università di Bari, Italy.
Bellantuono
V
V
Quaranta
A
A
Castronuovo
G
G
Cassano
G
G
Ardizzone
C
C
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D002712:Chlorides / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D009288:Naproxen / Q000494:pharmacology; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology; D011893:Rana esculenta / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D011722:Pyrethrins; D013449:Sulfonamides; D009288:Naproxen; C017967:W 7; D000584:Amiloride; D016572:Cyclosporine; D012964:Sodium; D019703:Calcineurin; C017690:fenvalerate