Mononuclear cell membranes: stabilization by reproterol and cromoglycate, destabilization by fenoterol and salbutamol.
Electron paramagnetic resonance (EPR) spectroscopy with spin labels 5- and 16-doxyl-stearic acid (DSA) was used to differentiate between actions of beta-agonists on human mononuclear cell membrane. Reproterol (CAS 13055-82-8), salbutamol (CAS 51022-70-9) and fenoterol (CAS 1944-12-3) compared to cromoglycate (CAS 15826-37-6) were used at concentrations of 10-100 nmol/l per 10(7) cells. With reproterol, order and polarity was not much changed, whereas salbutamol and fenoterol significantly destabilized the membrane to similar extent. Cromoglycate acted in a stabilizing fashion. With trypan blue exclusion, reproterol and cromoglycate showed stable values, whereas salbutamol and fenoterol augmented permeability. Thus, by conventional lipid spin labeling the discrimination between salbutamol and fenoterol could not be carried out. In contrast, previous lipid peroxidation studies in a model system had revealed a decrease by reproterol, no change by salbutamol and an increase by fenoterol. Also, using fenoterol, protein spin label 4-maleimido-TEMPO (2, 2, 6, 6-tetramethyl-1-piperidinyloxy) showed an increase of membrane rigidity of mononuclear cells. Moreover, mast cells of different origin were previously found tween beta-agonists. Reproterol in all tests behaved in a therapeutically profitable way. In conclusion, in addition to lipid spin labeling other methods and materials should be considered, to finally arrive at a more realistic differentiation between, for instance, salbutamol and fenoterol. The term "membrane (de) stabilization" should not generally be used without careful consideration of the type of cell/membrane in question.
Zimmer
Guido
G
Gustav Embden Center of Biological Chemistry, University of Frankfurt/Main, Germany.
Bernhörster
Markus
M
Pilz
Patrizius
P
Schuchmann-Fix
Jutta
J
Hüggelmeier
Rolf
R
Blüm
Nicole
N
Libertus
Herman
H
D000420:Albuterol / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004205:Cromolyn Sodium / Q000494:pharmacology*; D004338:Drug Combinations; D004578:Electron Spin Resonance Spectroscopy; D005280:Fenoterol / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000648:ultrastructure; D009921:Metaproterenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry; D013113:Spin Labels; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014343:Trypan Blue
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D011506:Proteins; D013113:Spin Labels; C014792:reproterol; D005280:Fenoterol; D009921:Metaproterenol; D013806:Theophylline; D014343:Trypan Blue; D004205:Cromolyn Sodium; D000420:Albuterol