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Volume 103, Issue 1
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Yoshihisa ITO1994 Volume 103 Issue 1 Pages 1-10
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSGABAA receptors of the mammalian central nervous system are ligand-gated Cl- ion channels and the sites of action of many pharmacologically important drugs. GABAA receptors were characterized using a potent antagonist, [3H] SR 95531, and agonists such as [3H] GABA and [3H] muscimol. Pretreatment of brain membranes with Triton X-100 or phospholipase A2 increased [3H] GABA and [3H] muscimol binding in the frontal cortex and cerebellum, whereas these treatments significantly decreased [3H] SR 95531 binding. The treatment of rats subacutely with a subconvulsive dose of bicuculline (2 mg/kg, i.p., daily for 10 days) significantly increased the apparent affinity for [3H]muscimol in the frontal cortex, cerebellum, striatum and substantia nigra. On the other hand, the apparent affinity for [3H] SR 95531 binding was significantly decreased in these regions. These results suggest that subacute bicuculline treatment in vivo and treatment in vitro of brain membranes with Triton X-100 or phospholipase A2 bring about a conformational change in the GABAA-receptor molecule, thus resulting in access increase of the GABA agonist and access decrease of the antagonist to GABAA receptors. In the cerebellum, the Bmax values of [3H] muscimol and [3H] SR 95531 binding and Vmax value of muscimol-stimulated 36Cl- uptake were significantly increased following subacute bicuculline treatment with no change in the frontal cortex, with this process involving increased de novo synthesis of GABAA receptors.View full abstractDownload PDF (21177K) -
Hitoshi ENDOU1994 Volume 103 Issue 1 Pages 11-17
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSSince a single nephron is a functional unit of the kidney, individual microdissec ted segments from the nephron would be ideal tissue samples for investigations on renal pharmacology. Several micromethods have enabled researchers to analyze the biochemical and pharmacological characteristics of these nephron segments. Miniaturized cuvettes containing microliter volumes of samples can be applied for general procedures of photometry like Lowry's protein determination. Fluorometry becomes a more sensitive method when enzymatic cycling systems of NAD/NADH or NADP/NADPH are combined, which have been used for assays of enzyme activities or substrate contents in minute biological samples having tissue proteins less than 1 μg. The microchemiluminescence procedure has been successfully utilized for cellular ATP content or oxygen radical generation. Radioimmunoassay can be used to determine endogeneous components such as cyclic nucleotides, eicosanoids, etc. Continuous gradient polyacrylamide microgels prepared in 5- to 10-μl capillaries have made it possible to quantify the intranephron distribution of cytochrome P-450, xanthine oxidase and superoxide dismutase. As an example of the modern techniques, microscopic fluorometry using Fura-2AM has been established to identify agonist-induced cytosolic free calcium transients.View full abstractDownload PDF (12320K) -
Tadashi NAGAMATSU, Noriyuki KOJIMA, Yoshio SUZUKI1994 Volume 103 Issue 1 Pages 19-26
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSWe investigated the effects of cyclosporin A (CyA) on accelerated passive Heymann nephritis, an experimental model of membranous nephropathy, that is characterized by immune complex deposition on the glomerular basement membrane. The nephritis was induced in rats by injection of antiserum against the antigen located in the renal tubular brush border membrane and sensitizaiton with rabbit γ-globulin. CyA was administered p.o. at the dose of 2.5, 10 or 20 mg/kg/day for 40 days after the injection of the antiserum. The administration of CyA resulted in marked supression of proteinuria and hypercholesterolemia in the nephritic rats. In light microscopy, nephritic control rats showed thickening of the glomerular basement membrane and spike formation in the glomeruli. CyA significantly reduced the appearance of the glomerular alteration. The production of antibody was dramatically attenuated by CyA administration. However, CyA did not decrease the number of circulating white blood cells and platelets below the normal level. In conclusion, CyA suppressed the progress of accelerated passive Heymann nephritis in a dose-dependent manner. The effect of CyA is likely attributable to the powerful depression of antibody production.View full abstractDownload PDF (17687K) -
Hiroshi MORIUCHI, Tomokazu YUIZONO1994 Volume 103 Issue 1 Pages 27-36
Published: 1994
Released on J-STAGE: February 06, 2007
JOURNAL FREE ACCESSWe constructed an oleic acid (OA)-induced PaO2 decrease model in guinea pigs. We then examined several basic conditions to establish the primary screening model to determine useful drugs for hypoxemia. Hartley strain guinea pigs were anesthetized with pentobarbital (25 mg/kg) and catheterized into the subclavian artery for blood sampling and for measuring blood pressure; they were also catheterized into the subclavian vein for drug administration. Then the animal was immobilized with pancuronium (0.1 mg/kg) and ventilated by a ventilator with room air. The following results were obtained: 1) there were no significant fluctuations of PaO2, PaCO2 and pH throughout the 11 sampling over a 2-hr period. Airway pressure and blood pressure also remained relatively constant. 2) Percentage of decrease in PaO2 by OA (15μl/kg) in the hyperventilated group was greater than that in the normally-ventilated group. 3) Increasing doses of 10, 15, 30 and 60 μl/kg of OA resulted in dose-dependently lower values of PaO2. 4) Tranexamic acid (2 g/kg, i.p.) significantly prevented the decrease in PaO2 at 10 and 15 min after OA (15 μl/kg) injection. 5) Procaterol hydrochloride (0.1 μg/kg, i.v.) failed to inhibit the decrease in PaO2 by OA (15 μl/kg). These results suggest that by using a suitable ventilation and OA dose, this model could be used as a primary screening model of drugs for hypoxemia and that tranexamic acid might bean effective drug for hypoxemia caused by a mechanism by which OA decreases PaO2.View full abstractDownload PDF (18673K)
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