Drug Tolerance in Biomembranes: A Spin Label Study of the Effects of Ethanol

Abstract

Ethanol in vitro increased the fluidity of spin-labeled membranes from normal mice. Membranes from mice that had been subjected to long-term ethanol treatment were relatively resistant to this fluidizing effect. The data suggest that the membranes themselves had adapted to the drug, a novel form of drug tolerance.

Alcohol stress, membranes, and chaperones

“…Membranes isolated from chronically ethanol-treated mice proved resistant to the fluidizing effect of ethanol (Chin and Goldstein 1977), and in parallel, the cholesterol content of the membranes was increased (Chin et al 1978). Chronic ethanol treatment also induced a significantly increased cholesterol level in microsomes isolated from chicken brain and liver (Sanchez-Amate et al 1991).…”

“…Enhanced cell membrane fluidity has been documented in different cell types after in vitro ethanol treatment. Ethanol treatment increases the fluidity of murine erythrocytes and synaptosomal and mitochondrial membranes in a dose-dependent manner (Chin and Goldstein 1977). Ethanol exerts a significant disordering effect on isolated erythrocytes, synaptic plasma membranes, and microsomal membranes of the murine brain (Armbrecht et al 1983).…”

Viability in Drosophila melanogaster in relation to age and ADH activity of eggs transferred to ethanol food

“…The nature of the induced ethanol tolerance is still obscure but the fact that the permeability of membranes can change under the influence of ethanol may be relevant (Chin and Goldstein, 1977).…”

Ethanol in Human Brain by Magnetic Resonance Spectroscopy: Correlation With Blood and Breath Levels, Relaxation, and Magnetization Transfer

“…Studies have shown that EtOH is likely to be found on the hydrophilic membrane surface or in protein pockets (Barry and Gawrisch, 1994;Chiou et al, 1992;Hitzeman et al, 1986;Klemm, 1998;Moxon et al, 1991;Rottenberg, 1987Rottenberg, , 1992 or, less likely, in the core of biological membranes, which show a relatively low partition coefficient for short chain alcohols such as EtOH (Barry and Gawrisch, 1994;Chiou et al, 1992;Klemm, 1998;Metcalfe et al, 1968;Rottenberg, 1992). The amount of macromoleculeassociated EtOH in membranes has been described to range from 6% to 90%, depending on the type of membrane investigated (Grenell, 1975;Kelly-Murphy et al, 1984;Nie et al, 1989;Rottenberg et al, 1981;Sarasua et al, 1989), and to be affected by chronic alcohol exposure (Beauge et al, 1985;Chin and Goldstein, 1977;Kelly-Murphy et al, 1984;Littleton and John, 1977;Rottenberg et al, 1981Rottenberg et al, , 1987Sarasua et al, 1989;Wood et al, 1987;reviewed in Rottenberg, 1992). The EtOH molecules in any of these molecular environments are restricted motionally, so that their T 2 relaxation times are extremely short (<1 msec).…”

“…Both mechanisms require EtOH molecules in close contact with brain macromolecules. Early electron spin resonance and fluorescence studies showed that the degree to which EtOH is associated with macromolecules (its solubility or partition into membranes) is altered in chronic alcoholism, which possibly explains resistance to acute effects of alcohol (Chin and Goldstein, 1977;Rottenberg et al, 1981). In addition, infrared studies have shown that the anesthetic action of alcohol is associated with EtOH's binding to membrane phospholipids (Chiou et al, 1992).…”