include "/home/remark/public_html/header_clinical.php"; ?>
De Lorenzo, Emple and Glaser, Journal of Neurochemistry (1977), 2169 reported that therapeutic concentrations of PHT decreased the level of phosphorylation of two specific proteins present in rat brain synaptosomal preparations. The authors suggest that some of the stabilizing actions of PHT on neuronal tissue, including its inhibition of post-tetanic potentiation, may be due to its effect on synaptosomal protein phosphorylation.
2169. De Lorenzo, R. J., Emple, G. P., and Glaser, G. H., Regulation of the level of endogenous phosphorylation of specific brain proteins by diphenylhydantoin, J. Neurochem., 28: 21-30,1977.
De Lorenzo, Antiepileptic Drugs: Mechanisms of Action (1980),1799 demonstrated that PHT, in therapeutic concentrations, inhibited the effects of calcium on calmodulin-dependent norepinephrine release, as well as phosphorylation of synaptic vesicle-associated proteins. Carbamazepine also inhibited neurotransmitter release and protein phosphorylation, but phenobarbital had no effect.
1799. De Lorenzo, R. J., Phenytoin: calcium- and calmodulin-dependent protein phosphorylation and neurotransmitter release, Antiepileptic Drugs: Mechanisms of Action, 399-414, Glaser, G. H., Penry, J. K. and Woodbury, D. M., Eds., Raven Press, New York, 1980.
Lazarev, Chernokhvostov, Kokoz, Freydin, Kosarsky and Saxon, Advances in Myocardiology (1982),2694 reported that PHT (5 µM) inhibited calcium activation of the inward rectifying potassium channels in frog atrium. The authors suggest that PHT's effect is due to inhibition of calcium-calmodulin-mediated protein phosphorylation.
2694. Lazarev, A. V., Chernokhvostov, V. V., Kokoz, Y. M., Calmodulin-dependent regulation of calcium-activated outward current in frog atrial membrane, Adv. Myocardial., 3: 95-105,1982.
De Lorenzo, Annals of Neurology (1984),2441 reviewing and extending the study of calmodulin systems, reported that PHT, carbamazepine and the benzodiazepines all inhibit calcium-calmodulin regulated protein phosphorylation and neurotransmitter release through a common binding site. The author suggests that calmodulin-mediated processes play a role in the development of abnormal excitability and that PHT and the other agents tested control hyperexcitability, including post-tetanic potentiation, by regulating these processes.
See also Refs. 2367, 2368, 2439, 2440.
De Lorenzo, R. J., Calmodulin systems in neuronal excitability: a molecular
approach to epilepsy, Ann. Neurol., 16: S 104-S114, 1984.
2367. Burke, B. E., De Lorenzo, R. J., Ca2+ and calmodulin-dependent phosphorylation of endogenous synaptic vesicle tubulin by a vesicle-bound calmodulin kinase system, J. Neurochem., 38(5): 1205-18, 1982.
2368. Burke, B. E., D Llorenzo, R. J., Ca2+ and calmodulin-regulated endogenous tubulin kinase activity in presynaptic nerve terminal preparations, Brain Res., 236: 393-415, 1982.
2439. De Lorenzo, R. J., Calmodulin in neurotransmitter release and synaptic function, Fed. Proc., 41(7): 2265-72, 1982.
2440. De Lorenzo, R. J., Calcium calmodulin protein phosphorylation in neuronal transmission: A molecular approach to neuronal excitability and anticonvulsant drug action, Advances in Neurology. Status Epilepticus, Delgado-Escueta, A. V., et al., Eds., Raven Press, New York, 325-38, 1983.
Advisoryinclude "/home/remark/public_html/footer.php"; ?>