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Volume 90 (2002)
- Issue 4 Pages 295-
- Issue 3 Pages 205-
- Issue 2 Pages 101-
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Volume 90, Issue 1
Displaying 1-14 of 14 articles from this issue
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Reviews
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Daniel C. Broom, Emily M. Jutkiewicz, Kenner C. Rice, John R. Traynor, ...Subject area: Infomation Science
2002 Volume 90 Issue 1 Pages 1-6
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSThe development of selective δ-opioid receptor agonists has revealed some very intriguing behavioral properties. δ-Opioid agonists have antinociceptive, seizuregenic and convulsive properties. A number of studies have identified a novel behavioral effect of δ-opioid-receptor agonists, implicating a role for the δ-opioid receptor in depression. Early clinical experiments demonstrated that exogenously administered opioid peptides had antidepressant activity in human patients. Also, enkephalinase inhibitors, which prevent the degradation of endogenous enkephalins, produced antidepressant-like effects mediated through the δ-opioid receptor in animal models of depression. More recently, the selective non-peptidic δ-opioid agonists SNC80 and (+)BW373U86 demonstrated antidepressant-like activity in the forced swim assay in rats. These studies propose that the δ-opioid receptor may provide a new therapeutic target for treating human depression.View full abstractDownload PDF (280K) -
Yuta Kobayashi, Hideki OkunishiSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 7-11
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSRheumatoid arthritis (RA) is a chronic inflammatory disease and its exact cause and pathophysiological process remain unclear. Fibroblast-like synoviocytes, macrophages and T lymphocytes are considered to be the major contributors in the pathophysiological process of RA; however, an increasing number of papers have drawn attention to the potential role of mast cells (MCs) in the process. In an animal model of RA, we reported an increase in MC numbers in the arthritic region, which agreed with the observation in human RA. In addition, a good correlation between the number of MCs and the development of disease was observed. However, there has been little experimental or clinical evidence of the beneficial effects of the modification of MC activity on the pathogenesis of RA and this is the weak point of the hypothesis. We therefore studied the effects of a MC-stabilizing compound, cromoglicate lisetil (CL), which is an orally deliverable prodrug of cromolyn sodium, on the RA disease model. The MC-stabilizer had efficacy in a mouse model. The beneficial effects of CL in this animal model further suggested the contribution of MCs in the pathophysiological process of RA. Concerning the contributive mechanism of MC on the pathogenesis of RA, our results using a disease model suggested that activation of MC chymase and matrix metalloproteinases might be involved. MC is now considered to be one of the targets of RA treatment.View full abstractDownload PDF (229K)
Full Papers
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Haruko Futagawa, Hiroaki Takahashi, Taku Nagao, Satomi Adachi-AkahaneSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 12-20
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESS2-sec-Butylphenyl N-methylcarbamate (BPMC) is a carbamate-type cholinesterase (ChE) inhibitor with unique toxicological properties such as noncholinergic cardiovascular collapse. Effects of BPMC on L-type Ca2+ channel currents (ICa(L)) were studied in isolated guinea pig ventricular myocytes using the whole-cell patch-clamp technique, since the examination of cardiovascular responses indicated its Ca2+ antagonistic action. BPMC induced bradycardic and hypotensive responses in vivo and inhibited contraction of isolated papillary muscles (IC50 = 1.3 × 10− 4 M) in guinea pigs. BPMC produced reversible block of ICa(L) in the concentration range of 10 −4 – 10 −3 M. At test potentials between −30 mV and +20 mV, BPMC at 3 × 10 −4 M caused marked acceleration of decay rate of ICa(L) with moderate reduction of peak ICa(L) amplitude. BPMC (3 × 10 −4 M) shifted the steady-state inactivation curve to the hyperpolarizing direction by 12.7 mV. Decay rate of Ba2+ currents (IBa(L)) was also accelerated by BPMC. Fitting analysis of inactivation kinetics of IBa(L) with a two-exponential equation revealed that BPMC accelerates the slow inactivation component. At concentrations for blocking peak IBa(L) by ca. 30%, the inactivation kinetics of IBa(L) were significantly accelerated by BPMC, but merely slightly accelerated by Ca2+ channel antagonists such as diltiazem, nifedipine, or verapamil. These results indicate that BPMC, in addition to the inhibition of ChE, blocks L-type Ca2+ channels by accelerating voltage-dependent inactivation.View full abstractDownload PDF (244K) -
Yasuhide Watanabe, Isao Matsuoka, Junko KimuraSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 21-27
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSWe investigated chronic effects of amiodarone on Na+/Ca2+ exchange current (INCX) and on the level of Na+/Ca2+ exchanger (NCX1) mRNA in guinea pig ventricular myocytes using the whole-cell clamp technique and RT-PCR analysis, respectively. Guinea pigs were intraperitoneally injected with 80 mg/kg per day of amiodarone or the vehicle (saline) for 1 or 4 weeks. Single ventricular cells were isolated from the hearts of both groups of animals. Action potential duration at 90% repolarization level was prolonged to 143% and 165% of the control values by treatment with amiodarone for 1 and 4 weeks, respectively. INCX density and the level of NCX1 mRNA were not significantly changed by chronic treatment with amiodarone. The level of thyroid hormone (T4) within the blood was not changed by the treatments. These results suggest that chronic treatment with amiodarone does not affect the Na+/Ca2+ exchanger, with respect to the level of its mRNA and current density in guinea pig ventricular myocytes.View full abstractDownload PDF (253K) -
Noriaki Makimoto, Yasuko Sakurai-Yamashita, Akira Furuichi, Shunsuke K ...Subject area: Infomation Science
2002 Volume 90 Issue 1 Pages 28-35
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSEffect of mosapride, a benzamide, on the motor activity associated with the release of endogenous acetylcholine (ACh) from enteric neurons was examined in the ileum of anesthetized dogs using an in vivo microdialysis method and compared with the effect of 5-hydroxytryptamine (5-HT). Intraarterial administration of 5-HT accelerated intestinal motor activity and increased the concentration of dialysate ACh, and the responses were inhibited by SB204070, a specific 5-HT4-receptor antagonist, but were apparently not affected by methiothepin, ketanserin and granisetron. Intraarterial administration of mosapride, a prokinetic benzamide, accelerated intestinal motor activity and the concentration of dialysate ACh increased. The effects of mosapride were antagonized by SB204070. Specific [125I]SB207710 binding was observed in the myenteric and submucosal plexuses and muscle layers of dog ileum by in vitro receptor autoradiography. High densities of [125I]SB207710 binding sites were detected in the myenteric and submucosal plexuses. Mosapride as well as SB204070 inhibited [125I]SB207710 binding. Thus, in the whole body of dogs, 5-HT and mosapride accelerated the intestinal motor activity due to the increases in ACh release mediated by stimulation of the 5-HT4 receptor.View full abstractDownload PDF (429K) -
Kazuhiko Oishi, Yoshitaka Takatoh, Jianjun Bao, Masaatsu K. UchidaSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 36-50
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSString-shaped reconstituted smooth muscle fibers were prepared in rectangular wells by thermal gelation of a mixed solution of collagen and cultured smooth muscle cells derived from the rat cerebral artery. The fibers contracted in response to KCl, 5-hydroxytryptamine (5-HT), noradrenaline, endothelin-1, endothelin-2, angiotensin II, prostaglandin F2α and prostaglandin E2. 5-HT-induced contraction was partially inhibited by the L-type voltage-dependent Ca2+ channel inhibitor nifedipine, putative non-selective cationic channel inhibitor SKF96365 and intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), and completely abolished by the myosin light chain kinase inhibitor ML-9. The fibers pre-contracted by 5-HT were completely relaxed by the Rho kinase inhibitor Y-27632, serine/threonine kinase inhibitor staurosporine, 8-bromo cyclic GMP and papaverine, and partially relaxed by dibutyryl cyclic AMP. Moreover, 5-HT as well as endothelin-1 and KCl enhanced 20-kDa myosin light chain phosphorylation in the fibers. These results suggested that the characteristics of contraction of the fibers reflect typical contractilities of vascular smooth muscle tissues. This technique will allow us to directly address questions relating to heterogeneity of receptor mechanisms and intracellular pathways of vascular smooth muscle contraction as a function of vessel type.View full abstractDownload PDF (517K) -
Emilio Ruiz, Eugenia Padilla, Teresa TejerinaSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 51-58
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSSomatostatin analogues are capable of inhibiting vascular smooth muscle and endothelial cell proliferation. However, little is known about the effect of somatostatin on vascular responses in endothelium-denuded coronary arteries in vitro. The aim of this work was to determine whether or not somatostatin prevented the contractile response induced by 5-hydroxytryptamine and acetylcholine in endothelium-denuded rabbit coronary arteries. Somatostatin attenuated the contraction produced by 5-hydroxytryptamine in both proximal (PC) and distal coronary (DC) arteries (contraction induced by 10−4 M 5-hydroxytryptamine was inhibited by 10−6 M somatostatin by 90.8 ± 11.0% (P<0.001, n = 9) and by 46.2 ± 14.0% (P<0.05, n = 9) in DC and PC, respectively), but concentration-dependently decreased the contraction induced by U46619 (11α-epoxy-methanoprostaglandin F2α) only in PC arteries, suggesting that the response of PC and DC arteries to somatostatin were qualitatively different. Furthermore, we suggest that somatostatin may enhance acetylcholine-induced relaxation by combination of increasing endothelium-dependent relaxation (by a NO-dependent mechanism) and blocking contraction at the muscle level.View full abstractDownload PDF (272K) -
Kazuhisa Kamata, Izumi Hayashi, Yoshito Mizuguchi, Katsuharu Arai, Tak ...Subject area: Infomation Science
2002 Volume 90 Issue 1 Pages 59-66
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSVarious proinflammatory mediators are believed to be involved in the processes and symptoms of ulcerative colitis (UC). To determine whether endogenous kinin enhances the severity of UC, we induced experimental colitis (EC) in kininogen-deficient mutant rats and tested the effect of a non-peptide B2 receptor antagonist. EC was induced in male kininogen-deficient Brown Norway-Katholiek rats (BN-Ka) and normal Brown Norway-Kitasato rats (BN-Ki) with 5% dextran sulfate sodium (DSS). Sprague-Dawley rats (SD) were also used. Colon length, body weight and hematocrit were determined for 7 days. Effects of FR173657, an orally active B2 antagonist, were tested. The colon length was shortened in BN-Ki with DSS treatment, but not in BN-Ka, and the difference between their lengths was significant. The hematocrit value was also reduced in BN-Ki, and the difference in hematocrit between BN-Ki and BN-Ka was significant. In SD, shortening of the colon and reduction in hematocrit were also observable, and both were blunted by FR173657. The survival rate in SD given DSS for 7 days was 68%, but FR173657 treatment restored it significantly to 100%. These results suggest that the endogenous kinins generated from the kallikrein-kinin system have a significant role in the development of EC.View full abstractDownload PDF (255K) -
Richard Sercombe, Christine Sercombe, Nicole Oudart, Jacques SeylazSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 67-76
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSThe modes of action of serotonin (5-HT) on the tone of the rabbit basilar artery were investigated in vitro with the aim of determining the exact role of the endothelium. After sacrificing the animal under pentobarbital anesthesia, 3-mm segments of the artery were removed and mounted in a 5-ml myograph for isometric tension recording. Vessels precontracted by histamine were relaxed by acetylcholine. Mean maximum relaxation at 10−4 M was reduced from 79% to 22% (P<0.001) by 10−5 M Nω-nitro-L -arginine (L -NA), and from 73% to 63% (NS) by 3×10−6 M indomethacin. Intact non-precontracted vessels were contracted by 5-HT (10−9 M to 10−5 M): 10−5 ML -NA significantly increased the contractile force (approximately twofold), whereas 3×10−6 M indomethacin significantly decreased it (to approximately 35%). In histamine-precontracted vessels, 5-HT induced at low concentrations (3×10−9 M to 3×10−8 M) a reduction in tone and induced an increase in tone at higher concentrations. At 10−5 M,L -NA abolished the relaxant phase of the response, whereas 3×10−6 M indomethacin potentiated it. In uridine triphosphate-precontracted segments, there was not a net reduction in tone under 5-HT at 3×10−9 to 3×10−8 M, but further contraction appeared at higher concentrations. The presence of 10−5 ML -NA significantly increased the contraction to 5-HT, but 3×10−6 M indomethacin did not significantly reduce it. Endothelial lesion reduced by about 50% the contractile response ofL -NA-treated arteries to 5-HT; and conversely, endothelial lesion increased approximately twofold the contraction of indomethacin-treated arteries to 5-HT. We conclude that 5-HT causes the release from the endothelium of two vasoactive factors, one of which is probably the vasodilator nitric oxide, but the size of the relaxation may depend on the prevailing level of nitric oxide synthase activation. The second factor is a cyclooxygenase-dependent contractile agent. However, the contraction to 5-HT was not modified by the presence of the thromboxane synthase inhibitor CGS 13080 (10−4 M), suggesting that thromboxane A2 is not the main contractile agent released.View full abstractDownload PDF (272K) -
Tamiko Suzuki-Nishimura, Masaatsu K. UchidaSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 77-80
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSThe production of prostaglandin D2 (PGD2) by rat peritoneal mast cells incubated with N-acetyl glucosamine (GlcNAc) oligomer-specific Datura stramonium agglutinin (DSA) for 10 min in the presence of 0.3 mM Ca2+ was examined. Previously, our group reported that the incubation of rat mast cells with DSA (5 – 100 μg/ml) under similar conditions resulted in a calcium influx and histamine release via a pertussis toxin-sensitive G-protein pathway of the mast cells, and the histamine release was inhibited by haptenic sugar chitooligosaccharides or GlcNAc-specific lectin wheat germ agglutinin (WGA) (K. Matsuda et al., Jpn J Pharmacol 66, 195 – 204 (1994)). DSA (5 – 100 μg/ml) dose-dependently stimulated the mast cells to generate PGD2. Chitooligosaccharides (1% w/v) and WGA (100 μg/ml) inhibited the production of PGD2 induced by 100 μg/ml of DSA, suggesting that the effect of DSA is sugar-specific. A prostaglandin G/H synthase inhibitor NS-398 (N-[cyclohexyloxy-4-nitrophenyl] methanesulfonamide) (10 μM) inhibited the formation of PGD2 induced by DSA (20 μg/ml). These results suggest that the binding of DSA to the corresponding sugar residues on the mast cell surface mediates the signaling of the prostaglandin G/H synthase pathway.View full abstractDownload PDF (163K) -
Jae Yeoul Jun, Cheol Ho Yeum, Yoo Whan Park, In Youb Jang, In Deok Kon ...Subject area: Infomation Science
2002 Volume 90 Issue 1 Pages 81-87
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSThe effects of arachidonic acid (AA) and the mechanism through which it modulates ATP-sensitive K+ (KATP) currents were examined in single smooth muscle cells of murine proximal colon. In the current-clamping mode, AA and glibenclamide induced depolarization of membrane potential. Using 0.1 mM ATP and 140 mM K+ solution in the pipette and 90 mM K+ in the bath solution at a −80 mV of holding potential, pinacidil activated the glibenclamide-sensitive inward current. The potential of these currents was reversed to near the equilibrium potential of K+ by 60 mM K+ in the bath solution. AA inhibited KATP currents in a dose-dependent manner. This inhibition was not changed when 1 mM GDPβS was present in the pipette. Chelerythrine, protein kinase C inhibitor, did not block the AA effects. Superoxide dismutase and metabolic inhibitors (indomethacin and nordihydroguaiacretic acid) of AA did not affect the AA-induced inhibition. Eicosatetraynoic acid, a nonmetabolizable analogue of AA, inhibited the KATP currents. These results suggest that AA-induced inhibition of KATP currents is not mediated by G-protein or protein kinase C activation. The inhibitory action is likely to be a possible mechanism of AA-induced membrane depolarization.View full abstractDownload PDF (207K) -
Yoshiko Iwasaki, Hideyuki Yamato, Hisashi Murayama, Takeshi Takahashi, ...Subject area: Infomation Science
2002 Volume 90 Issue 1 Pages 88-93
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSMenatetrenone (MK-4) inhibits bone resorption and enhances osteoblast-induced mineralization. In this study, we examined whether MK-4 administration had beneficial effects on osteoblast dysfunction and trabecular microstructure as well as on bone volume loss in a rat model of osteopenia. Male Sprague-Dawley rats were neurectomized and administered MK-4 as a daily supplement. On Day 21 after neurectomy, significant bone loss was observed in the positive control rats. MK-4 prevented the decrease in bone mineral density of the distal metaphysis of the femur. The osteoclast surface per bone surface (Oc.S/BS) and the number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and the mineral apposition rate (MAR) decreased in the immobilized rats on Day 42, suggesting suppression of bone turnover. In contrast, administration with a low dose of menatetrenone led to an increase of MAR and bone formation rate (BFR), while Oc.S/BS and N.Oc/B.Pm remained at normal levels. These data suggested that MK-4 reduced the loss of trabecular bone, prevented osteoblast dysfunction to a certain extent, and contributed to preservation of the trabecular microstructure in this rat model of osteopenia induced by sciatic neurectomy.View full abstractDownload PDF (113K)
Short Communications
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Yukiko Okamoto, Shinji Takai, Mizuo MiyazakiSubject area: Infomation Science
2002 Volume 90 Issue 1 Pages 94-96
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSWe investigated the preventive effect of an orally active chymase inhibitor, NK3201 (2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[{3,4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl]acetamide), on the adhesion formation in a hamster experimental model. Hamsters were administered orally once daily with 30 mg/kg of NK3201 or placebo from 3 days before uterus scraping to 7 days after it. A significant increase of chymase activity in the injured uterus was reduced by treatment with NK3201. The score of adhesion formations in the chymase inhibitor-treated group was significantly decreased in comparison with that in the placebo-treated group (P<0.01). Oral administration of NK3201 may be a useful drug for prevention of peritoneal adhesion formation.View full abstractDownload PDF (93K) -
Kazunori Mukai, Yuji Satoh, Akikazu Fujita, Tadayoshi Takeuchi, Norihi ...Subject area: Infomation Science
2002 Volume 90 Issue 1 Pages 97-100
Published: 2002
Released on J-STAGE: September 20, 2002
JOURNAL FREE ACCESSSince pituitary adenylate cyclase-activating polypeptide (PACAP) was shown to partially mediate nonadrenergic, noncholinergic (NANC) relaxation of longitudinal muscle of the proximal colon of ICR mice, we further studied the receptor subtype activated by PACAP by using a mutant mouse whose PAC1 receptors are markedly reduced. In wild-type mice, the PACAP-mediated component of NANC relaxation was 33%, but it was absent in the mutant mice. The potency of exogenous PACAP in inducing relaxation in the mutant mice was one hundredth of that in wild-type mice. VPAC1 and VPAC2 receptors were not suggested to have any role in the relaxation. These results suggest that PACAP mediates NANC relaxation of longitudinal muscle of mouse proximal colon via PAC1 receptors.View full abstractDownload PDF (142K)
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