Effect of calmodulin antagonists on calcium and ethanol-induced sleeping time in mice. 1985

D Sutoo, and K Akiyama, and K Iimura

This investigation was carried out to determine if calcium prolongation of ethanol-induced sleep is mediated by calmodulin and a calmodulin-dependent protein kinase. The duration of ethanol-induced sleeping time in ddY male mice was measured following the administration of CaCl2 (20, 40, 80 and 200 mumol/kg, intraperitoneally (IP) both with and without the calmodulin antagonists, W-7: [N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide] (4.2 micrograms/mouse, intraventricular (IVT) or trifluoperazine (TFP; 1.8 micrograms/mouse, IVT). When CaCl2 was administered in a dose dependent manner the duration of ethanol-induced sleep was prolonged. The prolongation was antagonized by W-7 and TFP. When mice were treated with W-7 or TFP together with serotonin (5-HT; 15 nmol/mouse, IVT), dopamine (DA; 30 nmol/mouse, IVT) or norepinephrine (NE; 30 nmol/mouse, IVT), the sleeping time induced by ethanol and calcium was enhanced. This finding suggests that W-7 and TFP selectively inhibit the synthesis of 5-HT, DA and NE, but they do not affect other neuronal functions of these biogenic amines. The results would suggest a probable mechanism in which Ca++ prolongs ethanol-induced sleeping time by activating tyrosine hydroxylase and tryptophan hydroxylase through intracerebral calmodulin and calmodulin-dependent protein kinase, which subsequently raise the levels of 5-HT, DA and NE.

UI MeSH Term Description Entries
D007276 Injections, Intraventricular Injections into the cerebral ventricles. Intraventricular Injections,Injection, Intraventricular,Intraventricular Injection
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002122 Calcium Chloride A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. Calcium Chloride Dihydrate,Calcium Chloride, Anhydrous
D002147 Calmodulin A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001679 Biogenic Amines A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. Amines, Biogenic,Biogenic Amine,Amine, Biogenic
D012890 Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Sleep Habits,Sleeping Habit,Sleeping Habits,Habit, Sleep,Habit, Sleeping,Habits, Sleep,Habits, Sleeping,Sleep Habit

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