Influence of gemfibrozil on sulfate transport in human erythrocytes during the oxygenation-deoxygenation cycle.
The effects of gemfibrozil (GFZ), an antihyperlipidemic agent, on the anionic transport of the human red blood cells (RBC) during the oxygenation-deoxygenation cycle were examined. Gemfibrozil clearly plays a role in the modulation of the anionic flux in erythrocytes; in fact it causes a strong increment of anions transport when the RBCs are in the high-oxygenation state (HOS). Such an effect is remarkably reduced in the low-oxygenation state (LOS). With the aim of identifying the dynamics of fibrate action, this effect has been investigated also in human ghost and chicken erythrocytes. These latter, in fact, are known to possess a B3 (anion transporter or Band 3) modified at the cytoplasmic domain (cdb3) which plays a significant role in the metabolic modulation of red blood cells. The results were analyzed taking into account the well-known interactions between fibrates and both conformational states of hemoglobin i.e. the T state (deoxy-conformation) and the R state (oxy-conformation). The effect of gemfibrozil on anionic influx appears to be due to a wide interaction involving a "multimeric" Hb-GFZ-cdb3 macromolecular complex.
Tellone
E
E
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Ficarra
S
S
Scatena
R
R
Giardina
B
B
Kotyk
A
A
Russo
A
A
Colucci
D
D
Bellocco
E
E
Lagana'
G
G
Galtieri
A
A
D000328:Adult; D002021:Buffers; D002138:Calibration; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D015248:Gemfibrozil / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011487:Protein Conformation; D013431:Sulfates / Q000097:blood*; D014638:Vanadates / Q000494:pharmacology
D002021:Buffers; D006454:Hemoglobins; D000960:Hypolipidemic Agents; D007202:Indicators and Reagents; D013431:Sulfates; D014638:Vanadates; D010749:Phosphoprotein Phosphatases; D015248:Gemfibrozil