title: Carrier-mediated uptake of methylglyoxal bis(guanylhydrazone) by rat lungs perfused in situ.
abstract: Rat lungs perfused in situ were employed to begin investigations of the pathways by which the tissue takes up circulating polyamines (PA). Uptake kinetics were studied using [14C]methylglyoxal bis(guanylhydrazone) (MGBG), a nonmetabolized substrate analogue thought to enter cells via the PA carrier. Lungs concentrated MGBG from the perfusate at a linear rate for at least 60 min. Uptake was saturable with respect to perfusate MGBG concentration; it exhibited an apparent Km of 12.5 microM and Vmax of 0.6 nmol X g lung-1 X min-1. MGBG (1 microM) uptake was inhibited rapidly and to a similar extent (30-40%) by the naturally occurring PAs spermidine, spermine, or putrescine (50 microM); no additional inhibition of uptake was exerted when all three compounds were present simultaneously (total concentration, 150 microM). No inhibition by 5-hydroxytryptamine was evident. Spermidine produced a half-maximal inhibitory effect at a perfusate concentration of 1.9 microM (vs. 1 microM MGBG). The spermidine-insensitive component of MGBG uptake operated at a Vmax similar to that of the control (total), 1.2 nmol X g-1 X min-1, but the apparent Km was increased 3.5-fold to 44 microM. These observations indicate that MGBG is taken up from the pulmonary circulation by a high-affinity, carrier-mediated, concentrative uptake process that is inhibited, at least in part, by naturally occurring polyamines.
mesh_terms: D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D006146:Guanidines / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008935:Mitoguazone / Q000378:metabolism*; D010477:Perfusion; D011652:Pulmonary Circulation; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D006146:Guanidines; D013096:Spermine; D012701:Serotonin; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine