piperidines and tempocholine

A method is presented to study the effect of drugs on membrane permeability. It is based on the reduction of a spin label trapped in the internal aqueous compartment(s) of membranes by ascorbate ions added to the bulk aqueous phase. The decay of the electron spin resonance signal of the spin label as a function of time gives an indication of the effect of added agents on the permeability of membranes. To demonstrate the technique, the effect on model membranes of egg phosphatidylcholine of the gout-implicated compound monosodium urate, the aprotic solvent dimethyl sulfoxide and the polyene antibiotic amphotericin B were examined. Monosodium urate did not affect the permeability, casting doubt on a proposed mechanism whereby the agent disrupts the membranes via hydrogen bonding. Dimethyl sulfoxide promoted a gradual increase in rate of solute passage across cholesterol-containing model membranes. Amphotericin B had a pronounced effect on the permeability of cholesterol-containing membranes, causing nearly total loss of paramagnetism immediately after addition. Some aspects of the mechanism of action of the drugs are discussed as well as the advantages and disadvantages of the method. The experiments also allow the evaluation of the effect of surface charge and cholesterol on the dimensions of model membranes.

Topics: Amphotericin B; Ascorbic Acid; Cell Membrane Permeability; Cholesterol; Choline; Cyclic N-Oxides; Dimethyl Sulfoxide; Electron Spin Resonance Spectroscopy; Kinetics; Liposomes; Oxidation-Reduction; Piperidines; Spin Labels; Uric Acid

Topics: Choline; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Erythrocyte Membrane; Erythrocytes; Hot Temperature; Humans; In Vitro Techniques; Parainfluenza Virus 1, Human; Piperidines; Spin Labels

The effect of ionizing radiation on the non-electrolyte, anion and cation permeability of the erythrocyte membrane was studied by measurement of the reduction rate of appropriate nitroxyl derivatives. Irradiation of bovine erythrocytes in the dose-range of 2-50 krad resulted in a regular dose-dependent increase in the reduction rates of a cation (TEMPO-choline) and a hydrophobic non-electrolyte (TEMPO), and non-regular changes in the reduction rate of a hydrophilic non-electrolyte (TEMPOL). The permeation constant for TEMPO-choline also showed a non-regular response to radiation, similar to the response pattern of other red blood cell parameters. These results also demonstrate that the effects of radiation on the transport of various solutes can be used as a means of distinguishing between different channels of membrane transport.

Topics: Animals; Biological Transport; Cattle; Choline; Cyclic N-Oxides; Dose-Response Relationship, Radiation; Erythrocyte Membrane; Erythrocytes; Extracellular Space; Gamma Rays; Kinetics; Mathematics; Piperidines; Spin Labels

Topics: Choline; Coliphages; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Escherichia coli; Kinetics; Piperidines; Spin Labels; Virus Replication