title: Saturable binding of anesthetics to nicotinic acetylcholine receptors. A possible mechanism of anesthetic action.
abstract: Recent controversies in the existence of saturable binding of general anesthetics in brain tissues prompted a careful examination of specific binding of anesthetics to neural receptors. We examined the binding of both local and general anesthetics using electron spin resonance and radioligand criteria. Our results suggested that the hydrophobic path, most probably through the lipid bilayer, figures importantly in the binding of the uncharged moieties of anesthetics. Competitive interactions by hydrophobic compounds for the high-affinity site in the nicotinic acetylcholine receptor led us to propose a hypothesis that includes a hydrophobic crevice of limited volume as part of the high-affinity site. Association of anesthetic at this crevice is in turn dependent on the anesthetic concentration in the lipid phase of the membrane. The hypothesis provides a mechanism for the saturable interaction of anesthetics with their protein target site in the membrane without violating the correlations expressed by the Meyer-Overton rule of anesthetic action.
authors.affiliation: Department of Biology, University of California, Santa Cruz 95064.
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: D D
authors.initials: DD
authors.lastname: Koblin
authors.forename: H H
authors.initials: HH
authors.lastname: Wang
mesh_terms: D000758:Anesthesia; D000777:Anesthetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D008954:Models, Biological; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013113:Spin Labels
chemical_list: D000777:Anesthetics; D011978:Receptors, Nicotinic; D013113:Spin Labels