Multiple Actions of Ethanol on Acetylcholine Receptors

Miller, Keith W.

doi:10.1007/978-1-4615-2470-0_8

Cited by 3 publications

(4 citation statements)

References 37 publications

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“…Alcohols appear to have two predominant actions on the nAChR. Ethanol and other short-chain n-alkanols potentiate ion current or ion flux through these receptor-channels (Dilger and Brett 1991;Miller 1993;Wu et al 1994). This potentiating effect has been observed in Torpedo electric organ and cell lines expressing mouse muscle nAChRs.…”

Section: Alcohol Effects On Ligand-gated Ion Channels: Pharmacologicamentioning

confidence: 99%

“…This potentiating effect has been observed in Torpedo electric organ and cell lines expressing mouse muscle nAChRs. Potentiation is most prominent at low agonist concentrations or when receptors are activated using a partial agonist (Miller 1993;Liu et al 1994;Wu et al 1994). Alcohols produce a leftward shift in the agonist concentration-response curve that indicates an increase in the apparent potency with which the agonist activates the receptor-channel complex (Forman et al 1989).…”

Section: Alcohol Effects On Ligand-gated Ion Channels: Pharmacologicamentioning

confidence: 99%

“…In addition to alcohol-induced potentiation of nAChR function, an additional channel-blocking action of alcohols has been described (Forman et al 1995;Miller 1993;Dilger and Brett 1991;Murrell and Haydon 1991;Wood et al 1995). This effect is especially prominent when the effects of longer-chain n-alkanols are examined.…”

Section: Alcohol Effects On Ligand-gated Ion Channels: Pharmacologicamentioning

confidence: 99%

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Alcohols and neurotransmitter gated ion channels: past, present and future

Lovinger

1997

Naunyn-Schmiedeberg's Arch Pharmacol

163

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The neurotransmitter-gated ion channels form a superfamily of neurotransmitter receptors specialized for recognizing transmitters and rapidly gating ion channels that are contained within the same holoprotein complex. A large body of research indicates that alcohols alter the function of this class of receptor at concentrations relevant to the intoxicating and anesthetic effects of the alcohols. In addition, studies have implicated several types of neurotransmitter-gated channels in intoxicating and anesthetic alcohol actions. All of the neurotransmitter-gated ion channels contain conserved features such as N-terminal ligand binding domains, hydrophobic membrane spanning domains and charged pore-lining domains. However, at least two, and possibly three families of receptors have been identified within the superfamily, including the nicotinic ACh-like receptors, the ionotropic glutamate receptors and the ATP-gated ion channels. This review will begin with a brief overview of the structural features of the different receptors, with an emphasis on comparing and contrasting features of the different families of neurotransmitter-gated channels. The emphasis will be mostly on the nicotinic-like receptors and the iGluRs, since more is known about these receptors than about other types of ligand-activated cation channels. The remainder of the review focuses on the latest studies aimed at determining the mechanism of alcohol actions on this superfamily of receptor-channels as well as the relationship between the molecular structure of these channels and the effects of alcohols on channel function. In addition, emerging directions for future study of these effects of alcohols and possible regions of the protein that may be altered during alcohol exposure are discussed.

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Section: Alcohol Effects On Ligand-gated Ion Channels: Pharmacologicamentioning

confidence: 99%

Section: Alcohol Effects On Ligand-gated Ion Channels: Pharmacologicamentioning

confidence: 99%

Section: Alcohol Effects On Ligand-gated Ion Channels: Pharmacologicamentioning

confidence: 99%

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Alcohols and neurotransmitter gated ion channels: past, present and future

Lovinger

1997

Naunyn-Schmiedeberg's Arch Pharmacol

163

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“…Ethanol alters the biological activity of various proteins (Deitrich et al, 1989;Wood et al, 1995;Miller, 1993). The molecular mechanism of how ethanol affects activity of proteins is not well-understood.…”

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confidence: 99%

Direct Binding of Ethanol to Bovine Serum Albumin: A Fluorescent and ¹³C NMR Multiplet Relaxation Study

et al. 1996

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Molecular mechanisms of ethanol interaction with proteins are not well-understood. In the present study, direct interaction of ethanol with hydrophobic binding sites on fatty acid free bovine serum albumin (BSA) was determined using the fluorescent probe 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS), cis-parinaric acid, and 13C NMR. The affinity of ethanol for BSA (Kd) was (5.21 +/- 0.31) x 10(-2) mol. Ethanol (25-200 mmol) competitively inhibited 1,8-ANS binding to BSA in a concentration-dependent manner with a Ki (concentration of ethanol that decreased 1,8-ANS binding by 50%) of 658 mmol. Preincubation of BSA with ethanol significantly decreased cis-parinaric acid binding to BSA, indicating interaction of ethanol with hydrophobic fatty acid-binding site(s) on BSA. Furthermore, ethanol was found to act on three of the five fatty acid-binding sites on BSA. These data indicated selectivity in the interaction of ethanol with hydrophobic sites on BSA. 13C NMR multiplet relaxation was used to characterize the interaction of ethanol with binding sites on BSA. Detailed analysis of [13C]ethanol relaxation data obtained in the presence of increasing BSA concentrations (25-200 mg/mL) led to the conclusion that the ethanol methyl group, as opposed to its hydroxyl group, binds in a hydrophobic pocket(s) on the protein. Ethanol-induced changes in activity of certain proteins may result from direct binding of ethanol to specific hydrophobic binding sites and/or displacement of endogenous ligands from those sites.

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Ethanol and the NMDA Receptor: Implications for Intoxication, Tolerance, Dependence, and Alcoholic Brain Damage

Lovinger

1996

Acamprosate in Relapse Prevention of Alcoholism

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Multiple Actions of Ethanol on Acetylcholine Receptors

Cited by 3 publications

References 37 publications

Alcohols and neurotransmitter gated ion channels: past, present and future

Alcohols and neurotransmitter gated ion channels: past, present and future

Direct Binding of Ethanol to Bovine Serum Albumin: A Fluorescent and ¹³C NMR Multiplet Relaxation Study

Ethanol and the NMDA Receptor: Implications for Intoxication, Tolerance, Dependence, and Alcoholic Brain Damage

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Multiple Actions of Ethanol on Acetylcholine Receptors

Cited by 3 publications

References 37 publications

Alcohols and neurotransmitter gated ion channels: past, present and future

Alcohols and neurotransmitter gated ion channels: past, present and future

Direct Binding of Ethanol to Bovine Serum Albumin: A Fluorescent and 13C NMR Multiplet Relaxation Study

Ethanol and the NMDA Receptor: Implications for Intoxication, Tolerance, Dependence, and Alcoholic Brain Damage

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Product

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About

Direct Binding of Ethanol to Bovine Serum Albumin: A Fluorescent and ¹³C NMR Multiplet Relaxation Study