Modulation of membrane transport of alkylating agents and XXXX by an analog of vasopressin in murine L5178Y lymphoblasts in vitro.

@entity7062 @entity1522 @entity1568 @entity137 @entity1160 @entity368 @entity535 @entity5 @entity786 @entity1877
The synthetic vasopressin analog @entity7062 ( @entity7062 ) has been shown to influence a wide range of cell-membrane-related events. Accordingly, the effect of @entity7062 on membrane transport of various alkylating agents and @entity1522 was evaluated in L5178Y lymphoblasts in vitro. @entity7062 stimulated melphalan uptake but conversely inhibited uptake of @entity1568 mustard, @entity1877 (the natural transport substrate for the @entity1568 mustard carrier), and @entity368 . No effect on the uptake of @entity786 or @entity1160 was observed. Increased melphalan uptake was due to effects on both substrate influx and efflux. The effect of @entity7062 on melphalan influx was particularly complex: @entity7062 stimulated melphalan influx by @entity535 transport system ASC but inhibited influx by system L, resulting in a net increase in unidirectional drug influx. Melphalan efflux was inhibited by @entity7062 . Decreased uptake of @entity1568 mustard, @entity1877 and @entity368 was due, at least in part, to decreased substrate influx. However, the mechanisms of inhibition were dissimilar: inhibition of substrate influx was non-competitive for @entity1877 but competitive for @entity368 . In conclusion, @entity7062 induced diverse but apparently specific effects on membrane transport of several alkylating agents and @entity1522 . Since the accumulation of alkylating agents such as melphalan within @entity5 cells is a major determinant of @entity137 , @entity7062 may have a role as a biological response modifier.
