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Volume 85 (2001)
- Issue 4 Pages 339-
- Issue 3 Pages 207-
- Issue 2 Pages 117-
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Volume 85, Issue 4
Displaying 1-15 of 15 articles from this issue
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Reviews
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Tiffany N. Heady, Juan C. Gomora, Timothy L. Macdonald, Edward Perez-R ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 339-350
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSOver the past few years increasing attention has been focused on T-type calcium channels and their possible physiological and pathophysiological roles. Efforts toward elucidating the exact role(s) of these calcium channels have been hampered by the lack of T-type specific antagonists, resulting in the subsequent use of less selective calcium channel antagonists. In addition, the activity of these blockers often varies with cell or tissue type, as well as recording conditions. This review summarizes a variety of compounds that exhibit varying degrees of blocking activity towards T-type Ca2+ channels. It is designed as an aid for researchers in need of antagonists to study the biophysical and pathological nature of T-type channels, as well as a starting point for those attempting to develop potent and selective antagonists of the channel.View full abstractDownload PDF (323K) -
Kenji Kitamura, Jun YamazakiSubject area: Infomation Science
2001 Volume 85 Issue 4 Pages 351-357
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSAlthough evidence of important contributions by Cl− channels to agonist-induced currents have been reported in vascular smooth muscle cells, the functional roles played by Cl− channels in the smooth muscle contraction and in setting the membrane potential remain essentially obscure. All of the admittedly few papers published have focused on the physiological roles of Cl− channels in the contraction and membrane depolarization elicited by agonists. At present, it seems likely that in vascular cells: a) Cl− conductance contributes to membrane depolarization, with the subsequent contraction being due to Ca2+ release from the intracellular store sites, and b) Cl− movements through the membrane of the Ca2+ store sites also regulate Ca2+ release and Ca2+ uptake from/into the store sites. As a Ca 2+-dependent Cl− current is most easily demonstrated under quasi-physiological conditions (by the perforated patch-clamp method), the contribution made by Cl− channels to smooth muscle function may be more important than previously thought. The development of the new, selective Cl−-channel blockers as well as the identification and gene engineering of the channel molecules are essential if we are to advance our knowledge of the physiology and pharmacology of the Cl− channels residing in vascular smooth muscle cells.View full abstractDownload PDF (542K)
Full papers
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Swapna Maity, Joseph Rajan Vedasiromoni, Lalima Chaudhuri, Dilip Kumar ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 358-364
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSThe aim of the present study was to investigate the underlying mechanism of the role of hot water extract of black tea [Camellia sinensis (L). O. Kuntze Theaceae] in normalizing the changes in intestinal transit and gastric emptying induced by various ulcerogenic agents in experimental rats. Intestinal transit as well as gastric emptying were significantly reduced in rats treated with glutathione (GSH) depleting agents, diethyl maleate (DEM), indoacetamide (IDA) and N-ethyl maleimide (NEM). Prior oral administration of black tea extract (BTE) at 20 ml/kg of a 10% solution, i.g. once a day for 7 days significantly increased the intestinal transit and gastric emptying with restoration of serum GSH level. Singular administration of succimer (60 mg/kg, i.g.), the standard sulfhydryl containing antiulcer agent used as a reference drug, was also effective. Increase in intestinal transit caused by BTE was reversed both by N-omega-nitro-L-arginine methyl ester (L-NAME) (25 mg/kg, i.p.) and N-omega-monomethyl-L-arginine (L-NMMA) (25 mg/kg, i.p.), but not with N-omega-nitro-D-arginine methyl ester (D-NAME) (25 mg/kg, i.p.). Furthermore, restoration of intestinal nitric oxide synthase (NOS) activity was found to be associated with BTE treatment. These results provide evidence that nitric oxide may play a role in BTE-mediated improvement of intestinal motility changes and gastric emptying induced by DEM, IDA and NEM.View full abstractDownload PDF (506K) -
Fatimunnisa Qadri, Thomas Arens, Eike C. Schwartz, Walter Häuser, ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 365-369
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSDuring development of hypertension in spontaneously hypertensive (SHR) rats, the activity of adrenal nitric oxide synthase (NOS) was investigated. SHR and Wistar-Kyoto (WKY) rats were studied at different ages: 3 - 4, 7 - 8 and 12 - 13 weeks after birth. Basal NOS activity was measured by the ability of homogenate to convert [3H]-L-arginine to [3H]-L-citrulline. At all ages, SHR rats exhibited 50 - 60% reduction in NOS activity when compared to age-matched WKY rats. In a following study, SHR rats (12 - 13 weeks) were treated chronically with the angiotensin I-converting enzyme inhibitors (ACE-I) captopril or enalapril, or the AT1-receptor antagonist losartan (2 × 25, 10 and 60 mg/kg per day for 10 days, respectively). The total NOS activity and protein expression of NOS isoenzymes from adrenals were determined. The basal NOS activity and protein expression of neuronal NOS (nNOS) was significantly increased in treated SHR rats when compared to control rats. The isoforms endothelial NOS and inducible NOS were undetectable. We conclude that impaired NO synthesis in the adrenal glands of SHR rats may contribute to the onset and maintenance of hypertension. The upregulation of nNOS protein in the adrenal glands may be one of the mechanisms by which ACE inhibitors and AT1-receptor antagonists by restoring the NO synthesis, mediate their antihypertensive effects.View full abstractDownload PDF (181K) -
Yasuhide Watanabe, Junko KimuraSubject area: Infomation Science
2001 Volume 85 Issue 4 Pages 370-375
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSWe examined the effect of bepridil, a class IV antiarrhythmic drug, on Na+/Ca2+ exchange current (INCX) in single guinea pig cardiac ventricular cells using the whole-cell voltage clamp technique. INCX was recorded by ramp pulses from the holding potential of −60 mV in the presence of 140 mM Na+ and 1 mM Ca2+ in the external solution and 20 mM Na+ and 119 nM free Ca2+ (7 mM Ca2+ and 20 mM BAPTA) in the internal solution. Bepridil suppressed INCX in a concentration-dependent manner. The IC50 value was 8.1 μM with a Hill coefficient of 0.8. Intracellular treatment with trypsin via the pipette solution attenuated the blocking effect of bepridil, suggesting that the inhibitory site is on the cytosolic side of the Na+/Ca2+ exchanger. In the absence of albumin in the external solution, 10 μM bepridil inhibited INCX by 46 ± 7% (n = 8), while bepridil blocked it by 28 ± 8% (n = 6) in the presence of albumin. Bepridil inhibited INCX in a supra-therapeutic concentration range.View full abstractDownload PDF (258K) -
Masahiro Kawamura, Akiyoshi Niitsu, Haruhisa Nishi, Eiji MasakiSubject area: Infomation Science
2001 Volume 85 Issue 4 Pages 376-381
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSWe examined the effect of extracellular adenosine 5'-triphosphate (ATP) on adrenocorticotropic hormone (ACTH)- and angiotensin II-induced steroidogenesis in bovine adrenocortical fasciculata cells. The low concentration of ATP (5 μM) potentiated ACTH-induced steroidogenesis synergistically. However, the purine derivative did not affect angiotensin II-induced steroidogenesis. Although adenosine (100 μM) (a metabolite of ATP) showed a weak steroidogenic effect, it did not potentiate ACTH-induced steroidogenesis. ATP also enhanced the steroidogenesis by NaF synergistically in bovine adrenocortical cells, but did not potentiate forskolin-and dibutyryl cyclic AMP-induced steroidogenesis. The stimulating effect of ACTH on cyclic AMP production was synergistically accelerated by ATP (5 μM), which has no effect by itself on cyclic AMP formation. These results suggest that extracellular ATP affected the ACTH receptor-adenylyl cyclase coupling processes, and potentiation of steroidogenesis by ACTH ensued in bovine adrenocortical fasciculata cells.View full abstractDownload PDF (210K) -
Yoshiaki Ohi, Kaoru Atsuki, Yuichi Torii, Yasushi Ohizumi, Minoru Wata ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 382-390
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSCa2+ release by caffeine and 9-methyl-7-bromoeudistomin D (MBED) and the concomitant activation of large conductance Ca2+-dependent K+ (BK) channels were analyzed using confocal Ca2+ imaging and whole cell voltage-clamp methods in guinea pig urinary bladder smooth muscle cells. Puff application of 3 or 10 mM caffeine for several seconds (2 - 5 s) elicited a large increase in intracellular Ca2+ concentration ([Ca2+]i) and induced a phasic outward current at a holding potential of −40 mV. The phasic outward current was the summation of spontaneous transient outward currents (STOCs) due to marked activation of BK channels and was followed by a short cessation of STOCs. Although the increase in superficial [Ca2+]i by caffeine was faster than that in global [Ca2+]i, the peak [Ca2+]i was identical in these areas. Puff application of 100 μM MBED also markedly enhanced STOCs for a few seconds. This response to MBED was not observed when stored Ca2+ was depleted by caffeine. The increase in [Ca2+]i by MBED occurred mainly in superficial areas. Longer application of 100 μM MBED for 2 min did not induce significant global [Ca2+]i increase but decreased the amount of Ca2+ release and cell shortening during the subsequent application of 10 mM caffeine. These results indicate that short application of MBED releases Ca2+ preferentially from superficial storage sites, presumably due to its slow approach to deeper sites. MBED may be a good pharmacological tool to manipulate selectively the superficial Ca2+ stores related to STOCs.View full abstractDownload PDF (621K) -
JongUn Lee, Ki Sup Yoo, Dae Gill Kang, Soo Wan Kim, Ki Chul ChoiSubject area: Infomation Science
2001 Volume 85 Issue 4 Pages 391-398
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSThe present study was performed to examine whether the gentamicin-induced urinary concentration defect is related to an altered regulation of aquaporin (AQP) water channels in the kidney. Male Sprague-Dawley rats were subcutaneously injected with gentamicin (20, 50 or 100 mg/kg per day) for 6 days. The protein expression of AQP1 - 3 channels and the catalytic activity of adenylyl cyclase were determined in the kidney. Gentamicin treatment resulted in renal failure associated with decreased tubular free water reabsorption and increased urinary flow rate. The expression of AQP2 proteins was significantly decreased in the kidney, in which the cortex was most susceptible, followed by the outer medulla and inner medulla in order. Gentamicin treatment also decreased the shuttling of AQP2, as evidenced by a decrease of its expression in the membrane fraction in proportion to that in the cytoplasmic fraction. The protein expression of AQP1 as well as that of AQP3 was also decreased in the cortex by treatment with the highest dose of gentamicin. The cAMP generation in response to arginine vasopressin or sodium fluoride was decreased by gentamicin, while that to forskolin was not significantly altered. These findings suggest that the primary impairment in the pathway leading to the generation of cAMP lies at the level of G proteins, resulting in a decreased expression of cAMP-mediated AQP channels. The gentamicin-induced urinary concentration defect may in part be accounted for by a reduced abundance of AQP water channels in the kidney.View full abstractDownload PDF (716K) -
Lian-Qing Guo, Masahiko Taniguchi, Qiao-Yun Chen, Kimiye Baba, Yasushi ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 399-408
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSTo investigate the possible drug interaction with herbal medicine, hot water decoctions or 40% ethanol infusions of several Umbelliferous or Citrus crude drugs and their prescriptions were examined in vitro for their abilities to inhibit human cytochrome P450 3A (CYP3A). Addition of each decoction or infusion from Baizhi (Angelica dahurica and varieties), Qianghuo (Notopterygium incisum or N. forbesii), Duhuo (Angelica biserrata), Fangfeng (Saposhnikovia divaricata), Danggui (Angelica sinensis), Zhishi or Zhiqiao (Citrus aurantium) resulted in various degrees of human CYP3A inhibition as determined by microsomal testosterone 6β-hydroxylation. The inhibitory potency was consistent with the abundance of the hydrophobic components for each sample. Experiments on the infusion of a Japanese Baizhi (BZ1) showed the major role of furanocoumarins on human CYP3A inhibition. Some of the crude drugs and a related prescription showed increased inhibition after the preincubation, suggesting the involvement of a mechanism-based inhibition. Some formulated prescriptions, however, showed intense inhibition with their hydrophobic fractions rather than with their hydrophobic fractions, suggesting that components other than furanocoumarins in herbal prescriptions may also cause CYP3A inhibition. These results indicate the necessity of intensive investigations on the possible drug interaction with traditional medicines.View full abstractDownload PDF (346K) -
Takeshi Nabe, Nobuaki Mizutani, Seiichi Osaki, Shingo Sugahara, Hirosh ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 409-415
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSWe have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.View full abstractDownload PDF (197K) -
Masakuni Noda, Takanori Matsuo, Hiroko Nagano, Masayuki Ohta, Masahiro ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 416-422
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSWistar fatty (WF) rats have a genetic predisposition to hyperglycemia, polyuria, hyperinsulinemia, hyperlipidemia, obesity and nephropathy. These phenotypic characteristics are similar to those observed in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. In this study, the effects of two types of renin-angiotensin system inhibitors, an angiotensin II type 1-receptor antagonist (AT1A) and an angiotensin I-converting enzyme inhibitor (ACEI), on renal injury in WF rats were studied during the progressive phase of diabetic nephropathy. An AT1A, candesartan cilexetil (1 mg/kg), and an ACEI, enalapril (10 mg/kg), were administered orally once a day for 12 weeks, beginning when the rats were 27-week-old and already showed diabetic nephropathy and obesity. Both drugs prevented an increase in proteinuria during the experimental period. Furthermore, after 4-week intervention, the levels of proteinuria were markedly lower in drug-treated rats. At the end of the experiment, both drugs prevented the development of glomerular lesions without affecting glucose metabolism and obesity. In conclusion, the inhibition of angiotensin II activity ameliorated both existing proteinuria and the progression of proteinuria, resulting in preservation of glomerular structure. Thus angiotensin II plays important roles in the development and the progression of nephropathy in genetically obese diabetic WF rats.View full abstractDownload PDF (590K) -
Yoshimitsu Matsui, Kenji Horiuchi, Kenji Yamamoto, Kazuo KanaiSubject area: Infomation Science
2001 Volume 85 Issue 4 Pages 423-433
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSR-755 (N-(2,6-diethylphenyl)-N'-[3-(2-methylphenyl)-6,7-dihydro-5H-cyclopenta[f][l]benzothiophen-2-yl]urea), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, has been characterized in vitro, ex vivo and in vivo. R-755 potently inhibited ACAT activities, with IC50 values from 2.5 to 64 nM, in rabbit intestinal microsomes and several cell lines (CaCo-2, THP-1 and J774A.1 cells). R-755 reduced serum cholesterol and triglyceride levels and liver cholesterol contents in cholesterol-fed rats, hamsters and rabbits. Rabbits were fed a high cholesterol diet for 2 weeks and further fed the same diet containing R-755 for 2 weeks. R-755 dose-dependently reduced cholesterol content and ACAT activity in the aorta. When phorbol 12-myristate 13-acetate-treated THP-1 and J774A.1 cells were incubated in the medium containing 20% of serum from rats administered R-755, the ACAT activities of the cells were inhibited. Rabbits were fed a high cholesterol diet for 8 weeks to establish aortic atherosclerosis and then fed a normal diet with or without R-755 for 8 weeks. R-755 dose-dependently reduced the surface area with atherosclerotic involvement and cholesterol contents in the aorta, although plasma cholesterol level did not differ from that in the control group. These results suggest that R-755 is a potent hypolipidemic agent and has a direct antiatherosclerotic activity at the arterial wall.View full abstractDownload PDF (653K) -
Kam-Ming Ko, Duncan H.F. Mak, Michel K.T. Poon, Ho-Yan YiuSubject area: Infomation Science
2001 Volume 85 Issue 4 Pages 435-442
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSThe effects of short-term (2-week) diabetes on myocardial ischemia-reperfusion (I-R) injury and associated changes in myocardial non-enzymatic antioxidant level were examined. Isolated-perfused hearts prepared from control and diabetic rats were subjected to increasing periods of ischemia and reperfusion, and myocardial I-R injury was assessed by measuring the extent of lactate dehydrogenase (LDH) leakage and contractile force recovery. While a brief period (20 min) of post-ischemic reperfusion caused a smaller extent of LDH leakage, the prolonged period (40 min) of reperfusion produced a greater degree of I-R injury in diabetic hearts, as indicated by the impaired recovery of contractile force. The apparent protection against I-R injury in diabetic hearts during the early phase of post-ischemic reperfusion was associated with increases in myocardial reduced glutathione/ascorbic acid and α-tocopherol levels, with the effect on α-tocopherol being most prominent. Insulin treatment could reverse the diabetes-associated changes in susceptibility to myocardial I-R injury and antioxidant response. The ensemble of results indicates that the myocardium isolated from short-term diabetic rat can produce a beneficial antioxidant response to I-R challenge, which may, in turn, be attributable to the decreased susceptibility to I-R injury observable during the early phase of reperfusion.View full abstractDownload PDF (548K) -
Tamiko Suzuki-Nishimura, Hideyuki Nakagawa, Masaatsu K. UchidaSubject area: Infomation Science
2001 Volume 85 Issue 4 Pages 443-452
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSA new sea urchin lectin from Toxopneustes pileolus, is D(+)galactose (Gal)-, D(+)fucose (Fuc)-specific. Incubation of rat peritoneal mast cells with the lectin in the presence of 0.3 mM CaCl2 for 10 min significantly and dose-dependently inhibited the histamine release induced by N-acetyl glucosamine (GlcNAc)-specific Datura stramonium agglutinin (DSA), an activator of the Gi-protein-dependent pathway in mast cells. This inhibition by the sea urchin lectin was sugar-specifically reversed in the presence of D(+)Gal or D(+)Fuc but not L(−)Fuc. The sea urchin lectin had no effect on the histamine release induced by compound 48/80, slightly inhibited the histamine release induced by substance P and mastoparan, and slightly enhanced the histamine release induced by melittin, but these effects were not dose-dependent. Compound 48/80, substance P, mastoparan and melittin are mast cell activators without sugar residues. It is suggested that the lectin binds to D(+)Gal residues of DSA to interfere with mast cell activation induced by DSA, a glycoprotein with arabinose and Gal residues. The effects of plant lectins with affinity to D(+)Gal, N-acetyl galactosamine and/or sialic acid and L(−)Fuc on the histamine release induced by DSA, compound 48/80 and substance P were also examined.View full abstractDownload PDF (620K)
Short Communication
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Kiyomi Miyake, Kaori Horikoshi, Yoshimi Ikeda, Akio Ishii, Akira Karas ...Subject area: Infomation Science
2001 Volume 85 Issue 4 Pages 453-456
Published: 2001
Released on J-STAGE: June 04, 2001
JOURNAL FREE ACCESSTo investigate the mechanism for the amelioration by olopatadine hydrochloride (olopatadine) of allergic rhinitis, we determined its effects on the increase of chemical mediator concentrations in nasal lavage fluid following the intranasal antigen challenge in guinea pigs actively sensitized with DNP-Ascaris. The concentrations of histamine and peptide-leukotrienes increased 10 min after the challenge. Olopatadine at 10 mg/kg (p.o.) significantly prevented the increase of histamine and tended to inhibit the increase of peptide-leukotrienes. The inhibition by olopatadine of the nasal symptoms seems to involve the inhibitory effect on the releases of histamine and, possibly, p-LTs into the nasal cavity.View full abstractDownload PDF (155K)
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