Mechanism of anesthesia: Anesthetics may restructure the hydrogen belts of membranes.
It is suggested that general anesthetics invade the "hydrogen belts" of neuronal plasma membranes, i.e. the regions of the bilayer containing hydrogen bond acceptors (CO of phospholipids) and donors (OH of cholesterol, sphingosin, ?-hydroxy fatty acids, proteins), and that they restructure the H-bond patterns between membrane lipids and proteins. The evidence is 2-fold. (1) The postulated existence of protein lipid hydrogen bonding has previously been demonstrated for glucose-6-phosphatase and for protein kinase C. (2) The prediction that changes in the H-bonding part of an anesthetic may influence its potency, but changes in the lipophilic part should not, can be verified. For a structurally widely varied group of monohydroxy compounds the range of anesthetic potency (inverse of intramembrane ED(50)(M) for loss of tadpole righting reflex) was smaller than 4-fold, while for n-hexane derivatives with different H-bonding headgroups the range of ED(50)(M) was about 100-fold. Although the results permit contributions by other factors they suggest that a restructuring of hydrogen belt H-bonding patterns is a general step in anesthesia.
Brockerhoff
H
H
New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, U.S.A.
Zingoni
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J
Brockerhoff
S
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