Carrier-mediated uptake of methylglyoxal bis(guanylhydrazone) by rat lungs perfused in situ

D. E. Rannels, J. L. Addison, A. E. Pegg

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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 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.

Original languageEnglish (US)
Pages (from-to)E292-E298
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume11
Issue number3
DOIs
StatePublished - 1985

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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