Solubilization of benzodiazepine receptors from long- and short-sleep mice.
Previous studies have shown that long-sleep (LS) and short-sleep (SS) mice, which were selectively bred for differential responses to the sedative-hypnotic actions of ethanol, also differ in response to several other agents that act at the GABAergic receptor. Binding at cortical benzodiazepine receptors is enhanced differentially by GABA and ethanol in membranes prepared from the two lines of mice with SS receptors enhanced to a greater extent. Heat denaturation studies and other biochemical characterizations of these receptors suggest that the GABAergic receptor complex from the two lines of mice differs. The present study examined whether perturbation of receptor-membrane interactions by treatment with detergent altered either GABA enhancement of [3H]flunitrazepam binding or ethanol enhancement of this binding. Octylglucopyranoside (OCTG), 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), or deoxycholate solubilization of cortical membranes resulted in a loss of the LS/SS difference in GABA enhancement. Ethanol's effects on binding were altered differently from those of GABA by treatment with OCTG as an increase, not a decrease, in enhancement was observed in both lines of mice. These results suggest that protein-membrane interactions play an important role in mediating LS/SS differences in the allosteric interactions within the GABAergic receptor complex.
Institute for Behavioral Genetics and School of Pharmacy, University of Colorado, Boulder, CO 80309.
J M
JM
Wehner
T Z
TZ
Bosy
L A
LA
Waltrip
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002793:Cholic Acids / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005445:Flunitrazepam / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects / Q000302:isolation & purification*; D012890:Sleep / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002793:Cholic Acids; D005960:Glucosides; D011963:Receptors, GABA-A; D003840:Deoxycholic Acid; C018619:octyl-beta-D-glucoside; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate