To explore the action mechanism of lithium in the brain, the author investigated the effects of lithium on Na-K ATPase and Ca ATPase in rat brain synaptosomes prepared from forebrains by the method of Booth and Clark. The activities of Na-K ATPase and Ca ATPase were assayed by the level of inorganic phosphate liberated from the hydrolysis of ATP. Lithium at the optimum therapeutic concentration of 1 mM decreased the activity of Na-K ATPase from the control value of 19.08 +/- 0.29 to 18.27 +/- 0.10 micromoles Pi/mg protein/h and also reduced the activity of Ca ATPase from 6.38 +/- 0.12 to 5.64 +/- 0.12 micromoles Pi/mg protein/h. The decreased activity of Na-K ATPase will decrease the rate of Ca2+ efflux, probably via an Na-Ca exchange mechanism and will increase the rate of Ca2+ entry by the depolarization of nerve terminals. The reduced activity of Ca ATPase will result in the decreased efflux of Ca2+. As a Conclusion, it can be speculated that lithium elevates the intrasynaptosomal Ca2+ concentration via inhibition of the activities of Na-K ATPase and Ca ATPase, and this increased [Ca2+]i will cause the release of neurotransmitters and neurological effects of lithium.
Animal ; Brain/*enzymology ; Ca(2+)-Transporting ATPase/*antagonists & inhibitors ; Lithium/*pharmacology ; Male ; Na(+)-K(+)-Exchanging ATPase/*antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Synaptosomes/*enzymology

Osteopontin (OPN) is a secreted phosphoprotein that is constitutively expressed in the normal kidney and is induced by various experimental and pathologic conditions. Several possible functions of OPN have been suggested, however the mechanism and significance of OPN expression are still uncertain. Since high salt concentration or salt crystal have been known to enhance OPN expression in intact kidney or cultured renal cells, in the present study we examined whether or not a low salt condition had an effect on OPN expression in the kidney. Adult male Sprague-Dawley rats were fed either a normal sodium or a sodium deficient diet for 1 week. Kidneys were processed for in situ hybridization using a digoxigenin-labeled riboprobe and for immunohistochemistry using antibodies to OPN, renin, and Na-K-ATPase. In rats fed a normal sodium diet, OPN mRNA and protein were expressed only in the descending thin limbs of Henle's loop (DTL) and in the papillary and pelvic surface epithelium (PSE). In rats fed a sodium deficient diet, there was a marked decrease in OPN immunoreactivity in the DTL, but no changes in PSE. In contrast, no changes were observed in OPN mRNA expression in the DTL by in situ hybridization, indicating that decreased OPN protein expression was a result of translational regulation. As expected, rats fed a sodium deficient diet were associated with increased immunoreactivity for Na-K-ATPase and renin compatible with activation of the renin-angiotensin system. These results suggest that dietary sodium may be involved in the regulation of OPN expression in the DTL of the rat kidney.
Animal ; Diet, Sodium-Restricted* ; Immunohistochemistry ; In Situ Hybridization ; Kidney/metabolism* ; Male ; Na(+)-K(+)-Exchanging ATPase/metabolism ; Rats ; Rats, Sprague-Dawley ; Renin/metabolism ; Sialoglycoproteins/metabolism ; Sialoglycoproteins/antagonists & inhibitors* ; Sodium/deficiency*

The present study was done to determine whether endogenous nitric oxide (NO) plays a role in the regulation of sodium transporters in the kidney. Male Sprague-Dawley rats were treated with NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking water) for 4 weeks. Control rats were supplied with tap water without drugs. Expression of Na, K-ATPase, type 3 Na/H exchanger (NHE3), Na/K/2Cl cotransporter (BSC1), and thiazide-sensitive Na/Cl cotransporter (TSC) proteins was determined in the kidney by Western blot analysis. Catalytic activity of Na,K-ATPase was also determined. The treatment with L-NAME significantly and steadily increased the systemic blood pressure. Total and fractional excretion of urinary sodium decreased significantly, while creatinine clearance remained unaltered. Neither plasma renin activity nor aldosterone concentration was significantly altered. The alpha1 subunit expression and the catalytic activity of Na, K-ATPase were increased in the kidney. The expression of NHE3, BSC1 and TSC was also increased significantly. These results suggest that endogenously-derived NO exerts a tonic inhibitory effect on the expression of sodium transporters, including Na, K-ATPase, NHE3, BSC1, and TSC, in the kidney.
Animals ; Blotting, Western ; Carrier Proteins/*biosynthesis ; Enzyme Inhibitors/pharmacology ; Kidney/drug effects/metabolism ; Male ; NG-Nitroarginine Methyl Ester/*pharmacology ; Na(+)-K(+)-Exchanging ATPase/biosynthesis ; Nitric Oxide Synthase/*antagonists & inhibitors/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Drug/biosynthesis ; Sodium/*metabolism ; Sodium Chloride Symporters/biosynthesis ; Sodium-Hydrogen Antiporter/biosynthesis ; Sodium-Potassium-Chloride Symporters/biosynthesis