Action of calcium channel and beta-adrenergic blocking agents in bilayer lipid membranes.
The action of beta-adrenergic blockers (propranolol, exprenolol, metoprolol, sotalol, atenolol, timolol) and calcium-channel blockers (verapamil, diltiazem) on the electrical properties and fluidity of bilayer lipid membranes (BLM and liposomes) has been investigated. When antibiotic ionophore substances were used as a probe, the electrical measurements showed that many of the drugs inhibited the cation transport across the membrane facilitated by the mobile carrier valinomycin, while having no significant effect on the cation transport through channels formed by gramicidin. The ability of the drugs to decrease the carrier-dependent membrane conductance was correlated to their partition into the lipid bilayer and the magnitude of transmembrane potential induced by them. In the TEMPO ESR spectral measurements, a number of beta-adrenergic and calcium blockers showed the fluidizing effect on liposomes composed of different lipids. The drug concentration required for a detectable change in TEMPO spectra parameter (f) was rather high (0.01 M verapamil), and the variation of pH from 6.5 to 3.0 did not affect the fluidizing effect of the drugs.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001692:Biological Transport; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D006096:Gramicidin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D009994:Osmolar Concentration; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013696:Temperature; D014634:Valinomycin / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D008051:Lipid Bilayers; D006096:Gramicidin; D014634:Valinomycin; D012964:Sodium; D011188:Potassium