|Budget Amount *help
¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1998 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1997 : ¥500,000 (Direct Cost : ¥500,000)
We investigated the effect of cis-Diamminedchlotoplatinum (CDDP ; Cisplatin) on electrolyte transport in rabbit cortical collecting ci, cts, using in vitro isolated tubular microperfusion method When CDDP was applied from the luminal side, 1) CDDP hyperpolarizedtransepithelial voltage(V_T) in a dose dependencymanner from 10^<-5> M to 10^<-3> M, by inhibiting potassium channel. This effect was reversible and V_T recoveredcompletely by washing out of drugs. 2) when alanine was eliminated from the perfusate andbath medium, luminal CDDPdepolanzed VT by inhibiting both of socium and potassium channels. These data lead us to conclub that luminal CDDP inhibits both of sodum andpotassium channel by differentmechanisms, in which the inhibition of sodium channel was abolished by the presence of alanine.
When CDDP was applied from the basolateral sida, 1) CDDP depolanzed VT in a cbse &pendent manner from 10^<-5> to 10^<-3> M.2) This depolarization was irreversible. 3) At aconcentrationof 10^<-4> and 10^<-3> M of CDDP, tubular swelling occurred in 60 mm and luminal membrane datachment was occurred in 90 mm. 3) When either of alanine, glycine or reduced glutathione (GSH) was added to the perfusate and bath medum, the changes of V_T was attenuated and at a concentration of 10A M CDDP, the presence of them completely abolished the depolarization. 4) However, so called antioxidant agents, such as L-NAME, catalase and dafferoxamine failed to abolished the effect of CDDP on V_T and morphological changes.
In the presence of L-buthionine-S,R-sulfoximine (BSO), a GSH synthesis inhibitor, the protective effect of both glycine and GSH cid not influenced however, in the presence of acivicine, gammer-transpepticbse inhibitor, the protective effectofOSH was inhibited, and the protective effect of glycine was preserved. These findings indicated that the intracellular concentration of glycine is the determinant of the protective effect, not the concentraion of GSH.