Pulmonary accumulation of methylglyoxal-bis(guanylhydrazone) by the oligoamine uptake system

The accumulation of methylglyoxal-bis(guanylhydrazone) (MGBG) into rat lung slices and its relationship to the accumulation of oligoamines has been investigated. MGBG was accumulated by rat lung slices by a process which obeyed saturation kinetics (Km 6.6 microM; Vmax 75.3 nmoles/g wet wt lung/hr). The uptake process appeared to be identical to those described for the accumulation of oligoamines and paraquat, being both KCN-(1 mM) and temperature-sensitive but insensitive to ouabain (100 microM). Pulmonary MGBG accumulation was found to be sodium-independent, either being enhanced or unaffected by sodium chloride-deficient media, so distinguishing the process from that described for the monoamine, 5-hydroxytryptamine. The ability and nature of various rat tissue slices to accumulate MGBG generally followed that of the oligoamines. Slices of lung, brain cortex and seminal vesicles accumulated MGBG by a KCN-sensitive and temperature-dependent process. These observations, together with the ability of MGBG to inhibit pulmonary oligoamine accumulation, indicate that it is the uptake system for the oligoamines which is mainly responsible for the in vitro accumulation of MGBG.