Cyclic nucleotides are important second messengers. Jedlitschky et al. expressed the human multidrug resistance protein 5 (MDR5) in hamster fibroblasts and showed that these cells exhibit an enhanced high-affinity ATP-dependent transport of cyclic nucleotides into inside-out membrane vesicles. The transport of cyclic guanosine monophosphate (cGMP) was faster and occurred at lower concentrations than that of cyclic adenosine monophosphate (cAMP), indicating that MDR5 is a high-affinity cGMP-specific pump. Also consistent with MDR5's being a cGMP-specific pump, membranes from MDR5-transfected cells did not transport glutathione or glucuronate conjugates, which are substrates for other isoforms of MDR protein. These findings have important implications for signaling both in terms of mechanisms for terminating cyclic nucleotide-mediated signaling cascades and for the possibility that exported cyclic nucleotides may initiate signal transduction in receptive cells.
Jedlitschky, G., Burchell, B., and Keppler, D. (2000) The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J. Biol. Chem. 275: 30069-30074. [Abstract] [Full Text]