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Title: Extracellular ATP stimulates an amiloride-sensitive sodium influx in human lymphocytes.
Austin Authors: Wiley, J S;Jamieson, Gary P;Mayger, W;Cragoe, E J;Jopson, M
Affiliation: Haematology Department, Austin Hospital, Heidelberg, Australia
Issue Date: 1-Aug-1990
Publication information: Archives of Biochemistry and Biophysics; 280(2): 263-8
Abstract: Extracellular ATP has been shown to increase the Na+ permeability of human lymphocytes by 3 to 12-fold. The kinetics of this ATP-induced response were studied by measuring 22Na+ influx into chronic lymphocytic leukemic lymphocytes incubated in low-sodium media without divalent cations. ATP-stimulated uptake of 22Na-ions was linear over 4 min incubation and this influx component showed a sigmoid dependence on ATP concentration. Hill analysis yielded a K1/2 of 160 microM and a n value of 2.5. The nucleotide ATP-gamma-S (1-2 mM) gave 30% of the permeability increase produced by ATP, but UTP (2 mM) and dTTP (2 mM) had no effect on 22Na influx. The amiloride analogs 5-(N-ethyl-N-isopropyl) amiloride and 5-(N,N-hexamethylene) amiloride, which are potent inhibitors of Na(+)-H+ countertransport, abolished 72-95% of the ATP-stimulated 22Na+ influx. However, the involvement of Na(+)-H+ countertransport in the ATP-stimulated Na+ influx was excluded by three lines of evidence. Sodium influx was stimulated 7-fold by extracellular ATP but only 2.4-fold by hypertonic conditions which are known to activate Na(+)-H+ countertransport. Addition of ATP to lymphocytes produced no change in intracellular pH when these cells were suspended in isotonic NaCl media. Finally ATP caused a membrane depolarization of lymphocytes which is inconsistent with stimulation of electroneutral Na(+)-H+ exchange. These data suggest that ATP acts cooperatively to induce the formation of membrane channels which allow increased Na+ influx by a pathway which is partially inhibited by amiloride and its analogs.
Gov't Doc #: 2369117
Journal: Archives of biochemistry and biophysics
Type: Journal Article
Subjects: Adenosine Triphosphate.pharmacology
Amiloride.analogs & derivatives.pharmacology
Biological Transport.drug effects
Dose-Response Relationship, Drug
Hydrogen-Ion Concentration
In Vitro Techniques
Leukemia, Lymphocytic, Chronic, B-Cell.metabolism
Lymphocytes.drug effects.metabolism
Membrane Potentials.drug effects
Sodium.antagonists & inhibitors.metabolism
Thymine Nucleotides.pharmacology
Uridine Triphosphate.pharmacology
Appears in Collections:Journal articles

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