Am. J. Respir. Cell Mol. Biol., Vol 10, No. 2, 02 1994, 160-166.
Multiple polyamine transport pathways in cultured pulmonary artery smooth muscle cells: regulation by hypoxia
SM Aziz, JW Olson and MN Gillespie
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, A.B. Chandler Medical Center, Lexington 40536-0082.
The polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) are a
family of low molecular weight organic cations that play essential
intracellular regulatory roles in cell growth and differentiation.
Consistent with this important function, increases in cellular polyamine
contents are necessary for a variety of physiologic and pathologic events
in the lung, including development of hypertensive pulmonary vascular
disease secondary to chronic alveolar hypoxia. In intact rat lungs, hypoxia
depresses ornithine decarboxylase activity, the initial rate-limiting
enzyme in de novo polyamine synthesis, and enhances uptake of PUT from the
vascular compartment, thus suggesting that increased polyamine transport is
the driving mechanism behind hypoxia-induced increases in lung polyamine
contents. Cultured bovine pulmonary artery smooth muscle cells (PASMCs)
also express a transport system for SPD that is augmented by culture under
hypoxic conditions. Because there may be multiple uptake pathways that are
relatively selective for specific polyamines, the present study determined
whether cultured bovine PASMCs expressed discrete transporters for
[14C]PUT, [14C]SPD, and [14C]SPM, and whether they were differentially
regulated by hypoxia. [14C]PUT, [14C]SPD, and [14C]SPM transport was
examined in PASMCs cultured under "standard" (culture medium PO2: > 100
torr), "normoxic" (culture medium PO2: 50 to 70 torr), or "hypoxic"
(culture medium PO2: 18 to 30 torr) conditions. Uptake of all three
[14C]polyamines in cells cultured under standard conditions was
temperature- and concentration-dependent, exhibited saturation kinetics,
and could be modeled by Michaelis-Menten kinetics. In hypoxic PASMCs,
values of Vmax for PUT, SPD, and SPM uptake increased by 3-, 2-, and
2-fold, respectively, relative to cells cultured under normoxic or standard
incubator conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
