Benzodiazepine inhibition of the calcium-calmodulin protein kinase system in brain membrane.
Benzodiazepines inhibit Ca2+-calmodulin-stimulated membrane protein phosphorylation. The effects of the benzodiazepines on protein phosphorylation are stereospecific and produced by membrane-bound benzodiazepine. The potency of benzodiazepine kinase inhibition is correlated with the ability of the benzodiazepines to inhibit electric shock-induced convulsions. These findings provide evidence that some of the anticonvulsant and neuronal stabilizing effects of benzodiazepines may be modulated by the Ca2+-calmodulin protein kinase system and indicate that this calmodulin-kinase system represents an identifiable benzodiazepine receptor in brain that is distinquishable by several criteria from the previously described high affinity benzodiazepine receptor.
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004789:Enzyme Activation; D007700:Kinetics; D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism; D011963:Receptors, GABA-A
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D002707:Chlordiazepoxide; D011494:Protein Kinases; D003975:Diazepam; D002118:Calcium