TY - JOUR
T1 - Carrier-mediated uptake of methylglyoxal bis(guanylhydrazone) by rat lungs perfused in situ
AU - Rannels, D. E.
AU - Addison, J. L.
AU - Pegg, A. E.
PY - 1985
Y1 - 1985
N2 - 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 K(m) of 12.5 μM and V(max) of 0.6 nmol·g lung-1·min-1. MGBG (1 μM) uptake was inhibited rapidly and to a similar extent (30-40%) by the naturally occurring PAs spermidine, spermine, or putrescine (50 μM); no additional inhibition of uptake was exerted when all three compounds were present simultaneously (total concentration, 150 μM). No inhibition by 5-hydroxytryptamine was evident. Spermidine produced a half-maximal inhibitory effect at a perfusate concentration of 1.9 μM (vs. 1 μM MGBG). The spermidine-insensitive component of MGBG uptake operated at a V(max) similar to that of the control (total), 1.2 nmol·g-1·min-1, but the apparent K(m) was increased 3.5-fold to 44 μM. 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.
AB - 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 K(m) of 12.5 μM and V(max) of 0.6 nmol·g lung-1·min-1. MGBG (1 μM) uptake was inhibited rapidly and to a similar extent (30-40%) by the naturally occurring PAs spermidine, spermine, or putrescine (50 μM); no additional inhibition of uptake was exerted when all three compounds were present simultaneously (total concentration, 150 μM). No inhibition by 5-hydroxytryptamine was evident. Spermidine produced a half-maximal inhibitory effect at a perfusate concentration of 1.9 μM (vs. 1 μM MGBG). The spermidine-insensitive component of MGBG uptake operated at a V(max) similar to that of the control (total), 1.2 nmol·g-1·min-1, but the apparent K(m) was increased 3.5-fold to 44 μM. 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.
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U2 - 10.1152/ajpendo.1985.248.3.e292
DO - 10.1152/ajpendo.1985.248.3.e292
M3 - Article
C2 - 3976883
AN - SCOPUS:0022038275
SN - 0193-1849
VL - 11
SP - E292-E298
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 3
ER -