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Volume 96 (1990)
- Issue 6 Pages 289-
- Issue 5 Pages 205-
- Issue 4 Pages 141-
- Issue 3 Pages 85-
- Issue 2 Pages 41-
- Issue 1 Pages 1-
Volume 96, Issue 2
Displaying 1-4 of 4 articles from this issue
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Takayoshi KUNO1990 Volume 96 Issue 2 Pages 41-47
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSProtein phosphorylation has been recognized as a major mechanism by which cellular functions are controlled by neurotransmitters and hormones. In this review, applications of molecular biological techniques to the analyses of regulatory mechanisms of protein phosphorylation by four major second messengers, cAMP, cGMP, diacylglycerol, and Ca2+, are described. 1) Complementary DNA of the regulatory subunit of the cAMP-dependent protein kinase was cloned and expressed in E. coli. Point mutations were introduced in order to analyze functional domains of the subunit. 2) The soluble isoform of guanylate cyclase was purified, and a cDNA of its 70-KD subunit was cloned. Cyclic GMP binding to purified cGMP-dependent protein kinase was characterized using a rapid filtration assay. 3) Primary structure of the catalytic subunit of calmodulin-dependent protein phosphatase (calcineurin A) was determined and the presence of the second isoform of the enzyme was shown by the cDNA cloning technique. 4) The regulatory domain of the protein kinase C was expressed in E. coli. Analysis using site-directed mutagenesis revealed that a “zinc finger”-like structure is responsible for the binding of phorbol esters. In these studies, the molecular biological approach has proven to be useful for clarifying the molecular mechanisms of cellular signal transduction related to second messengers and protein phosphorylation.View full abstractDownload PDF (5741K) -
Shinji UCHIDA, Masahiro ITOH, Meiko FUJIMOTO, Kimihiro YAMASHITA, Masa ...1990 Volume 96 Issue 2 Pages 49-63
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSEffects of betaxolol, a cardioselective β-adrenoceptor antagonist, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats (SHRSP) were investigated. Betaxolol was provided in a dose of 33±1.8 mg/kg/day, orally in drinking water, throughout the experimental period. The chronic treatment with betaxolol inhibited the development of hypertension in SHRSP and reduced values of blood urea nitrogen, creatinine, total cholesterol, free cholesterol, triglyceride, phospholipid and HDL-cholesterol in serum. Treatment with betaxolol apparently inhibited the incidence of hypertensive lesions such as cardiac fibrosis, mesenteric vasculitis, proliferative and/or necrotic vasculitis and glomeruli showing collapse or vasculitis in the kidneys. To shorten the time before the onset of hypertension and the subsequent stroke, SHRSP were kept on a SP diet containing 0.39% instead of the F-2 diet. When the SHRSP were kept on the SP diet, all of the control SHRSP had cerebral apoplexy and severe hypertensive lesions in the heart and kidney. When betaxolol was chronically administered to SHRSP, cerebral apoplexy and hypertensive lesions in the heart and kidney were inhibited, but the effect on blood pressure was slight. Treatment with betaxolol reduced serum creatinine levels. Our observations show that betaxolol reduces blood pressure and potently inhibits hypertensive complications in SHRSP.View full abstractDownload PDF (14313K) -
Toshihiko MORIMOTO, Yasuto MORIMOTO, Takemi FUKUDA, Michihide SETOGUCH ...1990 Volume 96 Issue 2 Pages 65-71
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSThe effect of Y-516 on the hyperactivity induced by dopamine injected bilaterally into the nucleus accumbens was compared with those of clocapramine (CCP), haloperidol (HPD) and chlorpromazine (CPZ). Dopamine (5-50 μg) injected into the nucleus accumbens induced a dose-dependent hyperactivity following pretreatment with nialamide (100 mg/kg, i.p., 2 hr). The hyperactivity induced by 10 μg of dopamine was antagonized by the i.p. administration of Y-516 (0.5-1.0 mg/kg), CCP (5-25 mg/kg), HPD (0.05-0.5 mg/kg) and CPZ (1-5 mg/kg) in a dose-dependent manner. The ED50 values of Y-516, CCP, HPD and CPZ were 0.85, 16.5, 0.098 and 2.53 mg/kg, respectively. These results suggest that Y-516 has a potential inhibitory effect on the mesolimbic dopaminergic system and may be a beneficial neuroleptic drugs.View full abstractDownload PDF (5055K) -
Yoshihiro MURAOKA, Hiroshi WATANABE, Shinji MATSUI, Hiroshi NARA, Hisa ...1990 Volume 96 Issue 2 Pages 73-83
Published: 1990
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSThis study examined the characteristics of urinary bladder lesions (cystitis) induced by ifosfamide (IF), an antitumor agent, and their inhibition by mesna in rats. Single i.v. doses of 50 mg/kg or more of IF induced cystitis characterized by increased bladder weight with mucosal hemorrhage and edema within 3 hr, with a plateau being reached 1 to 3 days after the injection. This change occurred earlier than myelotoxicity. Injection of IF to ureterligated rats did not induce the cystitis. Also, when IF was infused to one of a pair of rats in which the ureters had been crossed, the cystitis occurred only in the non-injected member of the pair whose bladder received urine flow from the IF-injected rat. Cystitis did not occur with direct injection of 10 mg of IF into the urinary bladder, but did with injection of the metabolite, 14 μg of acrolein. These findings show that IF-induced cystitis is not a systemic effect like myelotoxicity or an antitumor effect but a local effect. The cystitis could be completely inhibited by mesna, and this effect, which was dose-dependent, occurred from one-tenth of the IF dose. The effect was strongest when mesna was administrated within 1 hr of the IF injection. There was little difference in the effect between single and divided doses. The combined administration of IF with mesna did not lower the antitumor effect of IF.View full abstractDownload PDF (8797K)
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