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Volume 63 (1993)
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Volume 63, Issue 1
Displaying 1-18 of 18 articles from this issue
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Mitsutoshi Satoh, Noriko Kokubu, Issei Takayanagi1993 Volume 63 Issue 1 Pages 1-8
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSStudies on the displacement of [3H]prazosin binding by the α1-agonist phenylephrine revealed the presence of at least high and low-affinity binding sites in membrane preparations prepared from rabbit thoracic aorta. Although the low-affinity site was reduced by the pretreatment of tissues with chloroethylclonidine, this site was unaffected by the same pretreatment of membrane preparations that did not contain the GTP analog. However, in membrane preparations with the metabolically stable GTP analog GTPγ-S (10-5M) and single cell preparations, the low-affinity site was completely eliminated by the chloroethylclonidine pretreatment. Displacement studies with the α1-antagonist WB4101 also revealed high- and low-affinity binding sites labeled by [3H]prazosin. Displacement curves of WB4101 obtained from membrane preparations in the presence of GTPγ-S (10-5M) did not differ from those in the absence of GTPγ-S. These results suggest that the low affinity phenylephrine binding site labeled by [3H]prazosin was selectively bound by the chloroethylclonidine used to pretreat the tissues, membrane preparation containing GTPr-S and single cells, and that chloroethylclonidine is able to recognize these two distinct subtypes of α1-adrenoceptors only when GTPγ-S is present.View full abstractDownload PDF (507K) -
Tomihisa Kawasaki, Masao Katoh, Seiji Kaku, Hiroshi Gushima, Toichi Ta ...1993 Volume 63 Issue 1 Pages 9-16
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe thrombolytic activity of a novel modified t-PA, YM866, was compared with that of a recombinant t-PA in a canine model of copper coil-induced coronary thrombosis. The coronary thrombus was allowed to age for 1, 3 or 6 hr before either drug was administered. YM866 was administered by i.v. bolus injection, while t-PA was given by the same method, as well as by 60-min i.v. infusion. YM866 showed thrombolytic activity 2 to 4 times as potent as that of t-PA when administered by bolus injection, the difference in thrombolytic effect being obvious in the 3 and 6-hr-old thrombi. Coronary reperfusion was achieved more rapidly with YM866 than with i.v. infusion of t-PA. In animals injected with doses of more than 0.1 mg/kg of YM866, no acute reocclusion occurred. Depletion of plasma fibrinogen to 70% of baseline levels was observed in animals given 0.2 mg/kg YM866, 0.4 mg/kg t-PA by bolus, and 0.6 mg/kg t-PA via infusion. The residual plasma YM866 and t-PA antigen 30 min after bolus injection was 25% and 3% of the peak levels, respectively. YM866, administered by i.v. bolus injection, was thus confirmed to exert a thrombolytic effect superior to that of bolus injection and infusion of t-PA, without systemic fibrinolytic activation. These results suggest the potential clinical applicability of YM866 as a thrombolytic agent that can be administered by i.v.bolus injection for acute myocardial infarction.View full abstractDownload PDF (556K) -
Masao Endoh, Ikuo Norota, Masahiro Takanashi, Hideo Kasai1993 Volume 63 Issue 1 Pages 17-26
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe influence of protein kinase C (PKC) inhibitors, staurosporine, NA 0345 and H-7, on the α1- and β-adrenoceptor-mediated positive inotropic effect (PIE) was studied in rabbit ventricular myocardium. Staurosporine (1-10 nM), NA 0345 (10-100 nM) and H-7 (1-10 μM) selectively attenuated the PIE mediated by α1-adrenoceptors at concentrations that did not affect the β-mediated PIE and basal force of contraction. Staurosporine at higher concentrations (> 10 nM) decreased the basal force, while NA 0345 and H-7 did not. In membrane fractions derived from rabbit ventricular muscle, neither staurosporine, NA 0345 nor H-7 modified the specific [3H]prazosin binding at the concentrations that elicited the functional modulation. Accumulation of [3H]inositol monophosphate (IP1) induced by α1-adrenoceptor stimulation was not affected by the PKC inhibitors. Phorbol 12, 13-dibutyrate (PDBu), a PKC activator, also selectively attenuated the α1-mediated PIE, but in association with the inhibition of the α1-mediated IP, accumulation. Staurosporine (1 nM), but not H-7, antagonized the PDBu-induced inhibitory action on the a1-mediated PIE. These findings indicate that staurosporine, NA 0345 and H-7 produce a selective inhibition of the α1-mediated PIE, probably through inhibition of the α1-adrenoceptor-mediated activation of PKC. On the contrary, externally administered phorbol ester may act by uncoupling of α1-adrenoceptors to activation of phospholipase C through a pathway different from endogenous diacylglycerol to lead to a selective inhibition of the α1-mediated PIE.View full abstractDownload PDF (705K) -
Ikuo Kawamura, Tamotsu Mizota, Elizabeth Lacey, Yoshio Tanaka, Toshita ...1993 Volume 63 Issue 1 Pages 27-34
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effects of a new antiestrogen, droloxifene (DROL, (E)-α-[p-[2-(dimethylamino)ethoxy]-phenyl]-α''-ethyl-3-stilbenol), on human breast cancer cells in vitro and in vivo were studied. Since phenol red has a binding affinity to the estrogen receptor (ER), we studied the activities of drugs in medium with or without this indicator. Estradiol-17β (E2) stimulated the growth of ER-positive breast cancer cells, MCF-7, ZR-75-1 and T-47D, in medium without phenol red, but not in medium containing this indicator. In medium without phenol red, DROL had no marked effects on the growth of MCF-7 and ZR-75-1, but slightly stimulated the growth of T-47D. Tamoxifen (TAM) stimulated the growth of these 3 cells. DROL dose-dependently inhibited the E2-induced stimulation of growth of these cells in medium without phenol red, but TAM inhibited the growth only at high concentrations. The growth of ER-negative breast cancer cells, MDA-MB-231, was not influenced by E2, DROL or TAM. DROL was more effective than TAM against ER-positive Br-10 breast carcinoma in nude mice, but neither drug had effects on ER-negative MX-1 breast carcinoma. These results suggest that DROL shows an antitumor effect on ER-positive breast cancers, being less estrogenic and more antiestrogenic than TAM.View full abstractDownload PDF (542K) -
Katsuhiko Harada, Yuzo Fukata, Atsushi Miwa, Soichiro Kaneta, Hideaki ...1993 Volume 63 Issue 1 Pages 35-39
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe antianginal effect of KRN2391, N-cyano-N''-(2-nitroxyethyl)-3-pyridinecarboximid-amide monomethanesulfonate, on various anginal models in rats was compared with those of nifedipine and nicorandil. Angina pectoris was induced by methacholine or isoproterenol, and the change in the ST-segments in the electrocardiogram (ECG) was used as the parameter to indicate angina pectoris. The intracoronary administration of methacholine (3 μg) produced an elevation in the ST-segment of the ECG. This ST-elevation was inhibited by the intravenous administration of KRN2391 (30 and 100 μg/kg), nifedipine (100 and 300 μg/kg) and nicorandil (1000 and 3000 μg/kg). The administration of isoproterenol (10 μg/kg/min, i.v.) produced a depression of the ST-segment of the ECG. The intravenous administration of KRN2391 (100 μg/kg), nifedipine (100 μg/kg) and nicorandil (3000 μg/kg) inhibited the ECG changes induced by isoproterenol. These results suggest that KRN2391 exerts a potent protective effect on angina pectoris models compared with nifedipine and nicorandil. KRN2391 appears to be useful as an antianginal drug.View full abstractDownload PDF (334K) -
Shinya Yamanaka, Hiroshi Iwao, Tokihito Yukimura, Shokei Kim, Katsuyuk ...1993 Volume 63 Issue 1 Pages 41-45
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSIt has been reported that there is a continuous release of nitric oxide (NO) that contributes to the regulation of vascular tone in the arterial system. In contrast, the role of NO on vascular tone in the venous system is controversial. We examined the effect of NG-nitro-L-arginine (LNNA), an NO synthase inhibitor, on venous tone in dogs. Venous tone was evaluated by effective vascular stiffness (EVS), which was calculated from the changes in central venous pressure recorded simultaneously with changes in blood volume. LNNA (10 mg/kg, i.v.) increased EVS from 0.21±0.04 to 0.30±0.03 mmHgl kg/ml as well as increasing the systemic vascular resistance. NG-Nitro-D-arginine had no effect on EVS. The LNNA-induced increase in EVS was partly reversed by L-arginine, but not by D-arginine, indicating that the increase in EVS was attributable to a blockade of NO synthesis. Since the present study was conducted under ganglion blockade, nitroxidergic nerve terminals do not seem to be the source of NO in this case. These findings suggest that NO (endothelium-derived relaxing factor) is constantly released in the venous system and contributes to the regulation of total systemic venous tone.View full abstractDownload PDF (357K) -
Masaaki Kanashiro, Tatsuaki Matsubara, Toshio Goto, Nobuo Sakamoto1993 Volume 63 Issue 1 Pages 47-52
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSABSTRACT-A Cypridina luciferin analog (CLA), considered to be a sensitive and specific agent for the assay of superoxide, was assessed in isolated hearts for its effects on ischemia/reperfusion injury. Hearts of anesthetized male Wistar rats were isolated and perfused with a modified Krebs-Henseleit bicarbonate buffer to serve as non-recirculating working heart preparations. After 15 min of perfusion to achieve stability, they underwent 20 min of global ischemia and were then reperfused for 30 min with or without 250 μM of CLA, dissolved in the perfusate. The incidence of ventricular fibrillation was only 13% in the CLA group, whereas it was 88% in the controls. The CLA treatment was further associated with significantly increased left ventricular developed pressure and cardiac output; and in contrast, the left ventricular end-diastolic pressure was significantly reduced, as compared with the control group. Thiobarbiturate reacting substance content in the hearts of the CLA group was significantly decreased (27.5±2.4 versus 36.9±9.7 μmol/g dry weight). This study thus indicates that CLA may be useful for alleviating ischemia/reperfusion injury (reperfusion-induced arrhythmia and damage to heart function) involving free radicals.View full abstractDownload PDF (417K) -
Norifumi Yonehara, Fa-Di Tang, Reizo Inoki1993 Volume 63 Issue 1 Pages 53-58
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effects of morphine on the release of immunoreactive substance P (iSP) into the subcutaneous perfusate and the changes in cutaneous blood flow (CBF) elicited by antidromic stimulation of sectioned sciatic nerve were investigated in the instep of the hind paw of rats. Antidromic stimulation of the sectioned sciatic nerve induced a marked increase in iSP release into the subcutaneous perfusate and a biphasic flow response consisting of an initial transient decrease followed by an increase. Both the iSP release and the increase of the CBF evoked by antidromic stimulation (the second phase) were significantly inhibited by intra-arterial (i.a.) infusion of morphine (30 μmol/kg). These inhibitory effects of morphine were antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The i.a. infusion of SP (0.25 μmol/kg) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. Neither phase induced by i.a. infusion of SP was affected by preinfusion of morphine (10 or 30 μmol/kg, i.a.). We suggest that morphine applied locally mainly acts on the peripheral endings of small-diameter afferent fibers, not on blood vessels, and that activation of this site is involved in the regulation of the microcirculatory hemodynamics of cutaneous tissue through inhibition of SP release.View full abstractDownload PDF (404K) -
A.F.M. Mohibur Rahman, Masakatsu Takahashi, Hiroshi Kaneto1993 Volume 63 Issue 1 Pages 59-64
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe have examined whether or not the presence of pain can block the development of tolerance to morphine antinociception in mice. A single injection of formalin or Freund complete adjuvant into the dorsal part of one side of the hind paw resulted in a significant swelling of the treated paw which lasted more than 5 days. In formalin-treated animals that received the initial morphine 2 hr after the stimulant, the development of tolerance to morphine was delayed without affecting morphine antinociception when the effect was measured daily by the tail-pinch (TP) method but not by the tail-flick (TF) method. However, the stimulant suppressed tolerance development even in the TF method unless the daily measure ment was undertaken. When morphine injection was started from 5 days after the formalin injection, tolerance developed in a pattern similar to that in the control animals. On the other hand, treatment with Freund adjuvant did not affect the development of tolerance measured by both the TP and TF methods, with or without daily measurement of antinociception. When acetic acid was used as a stimulant, daily morphine was administered before or after the acetic acid injection, in the presence or absence of pain, tolerance developed to the same extent as in the control group, regardless of the time of morphine injection. Thus, our results suggest that the development of tolerance to narcotics may be modified by various factors, such as the type and intensity of nociception; and they also suggest that different results may be produced depending on the test method.View full abstractDownload PDF (389K) -
Norihisa Inazu, Tomoko Fujii1993 Volume 63 Issue 1 Pages 65-71
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSTo examine the role of carbonyl reductase (CR) in the development and function of testis, age-related changes in CR and the effect of exogenous calcium on CR in rat testis were studied. Testicular CR activity was the highest at 3 weeks of age when the enzyme activity was measured at 2, 3, 4, 8 and 20 weeks of age. The intensity of positive protein bands in testicular cytosol was similar among these age groups in Western blot analysis with anti-rat ovarian CR antibody. In 3-week-old rats, intravenous administration of 4 mg/kg calcium markedly suppressed the activity to about 50% of the control level 1 min after the treatment. Pretreatment with nicardipine prevented the inhibitory effect of exogenous calcium on the testicular CR activity in 3-week-old rats, indicating that the supressing action of calcium on the enzyme activity was mediated by the entry of extracellular calcium via calcium channels. There were no significant changes in the CR activity following the treatment with calcium and nicardipine in the other 3 age groups examined. These findings suggest that testicular CR plays an important role in the functional development of the testis during the infantile period in rats.View full abstractDownload PDF (521K) -
Katsumasa Kobayashi, Jun Hiroi, Shinichi Kishi, Kumi Sawase, Yoshitaka ...1993 Volume 63 Issue 1 Pages 73-81
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effects of a new antiallergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido)tetrazolate monohydrate], were studied and compared with those of tranilast, amlexanox, pemirolast, repirinast and disodium cromoglycate (DSCG) in experimental allergic models. Quinotolast potently inhibited such type I allergic reactions as passive cutaneous anaphylaxis (PCA) and anaphylactic bronchoconstriction in rats by both intravenous and oral dosing. All of these effects were stronger than those of the reference drugs tested. Quinotolast inhibited histamine release from rat peritoneal cells, but it had no antagonistic effect on histamine-, serotonin-, platelet activating factor- or bradykinin-induced cutaneous reactions in rats. Moreover, it was clearly demonstrated that quinotolast and DSCG had a cross tachyphylaxis to inhibit PCA in rats, suggesting that these drugs, at least in part, share the same mechanism of action. Furthermore, quinotolast potently inhibited PCA in guinea pigs in which DSCG and other reference drugs showed poor inhibitory activity. Quinotolast also showed stronger inhibitory effects on histamine and peptide leukotrienes release from guinea pig lung fragments or mouse cultured mast cells than the other drugs tested. Thus, the effect of quinotolast on type I allergic reaction would seem to be based on an inhibition of mediator release from inflammatory cells including mast cells. The results suggest that quinotolast will be beneficial in the treatment of type I allergy-related diseases.View full abstractDownload PDF (635K) -
Hisayuki Ohata, Toru Kawanishi, Megumi Kawanishi, Chikako Uneyama, Mic ...1993 Volume 63 Issue 1 Pages 83-91
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe cytoplasmic free calcium ion concentration ([Ca2+]i) of cultured guinea pig ileum longitudinal muscle cells loaded with a fluorescent [Ca2+]i indicator, fura-2, was measured by digital ratio imaging microscopy. Spontaneous [Ca2+]i oscillations were observed in 25% to 80% of the cells, which differed with the batches of the cultured cells after 5 to 8 days in culture. The frequency and amplitude of the [Ca2+]i oscillations in each individual cell were usually regular, but heterogeneity between neighboring cells was observed. The spontaneous [Ca2+]i oscillations were also observed even after incubation of the cells under a serum-free condition for 72 hr. Exchange of extracellular solution to Ca2+-free solution containing EGTA or BAPTA immediately stopped the [Ca2+]i oscillations. The ratio of the oscillating cells was dependent on the extracellular calcium ion concentration ([Ca2+]o); and heterogeneity in the range of the [Ca2+]o to generate the [Ca2+]i oscillations was observed. An inorganic Ca2+-antagonist, LaCl3, immediately suppressed the [Ca2+]i oscillations, but the treatment with verapamil or nicardipine, Ca2+-channel blockers, did not have any effect on the [[Ca2+]i oscillations. An inhibitor of the intracellular Ca2+ pump, thapsigargin, induced a transient increase in [Ca2+]i and then inhibited the spontaneous [Ca2+]i oscillations. Neomycin, a compound known to inhibit phosphoinositide turnover, inhibited the [Ca 21]i oscillations. These results suggest the following: (1) The generation of the spontaneous [Ca2+]i oscillations is highly dependent on [Ca2+]o but not due to Ca2+ influx through voltage-dependent Ca2+ channels; (2) Thapsigargin-sensitive Ca2+ pumping pools, which may be inositol 1, 4, 5-trisphosphate (IP3)-releasable Ca2+ pools, play an important role in generating the spontaneous [Ca2+]i oscillations, and the uptake of Ca2+ into the pools is highly dependent on Ca2+ influx across the plasma membrane.View full abstractDownload PDF (643K) -
Hidenobu Yuki, Keiji Miyata, Takeshi Kamato, Akito Nishida, Hiroyuki I ...1993 Volume 63 Issue 1 Pages 93-99
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe examined the contribution of the histamine H2-receptor to the histamine-induced wheal response in squirrel monkeys and guinea pigs. Intradermal injection of histamine, 2-pyridylethylamine (a selective H1-agonist), and dimaprit (a selective H2-agonist) dose-dependently induced the wheal response in squirrel monkeys and guinea pigs, although the reaction to dimaprit was much weaker than that to the other agonists. Chlorpheniramine dose-dependently depressed the wheal response in squirrel monkeys and guinea pigs at doses of 0.03-1 mg/kg and 0.03-3 mg/kg, p.o., respectively. However, famotidine, ranitidine and cimetidine had no effect at doses up to 30, 100 and 300 mg/kg, p.o. in guinea pigs and up to 1, 10 and 400 mg/kg, p.o. in squirrel monkeys, respectively. Cimetidine (3-300 mg/kg, p.o.) dose-dependently potentiated the inhibitory effects of chlorpheniramine (0.1 mg/kg, p.o.) in guinea pigs, but had no effects in squirrel monkeys. Famotidine and ranitidine did not alter the response to chlorpheniramine in either animal. These results suggest that the histamine H2-receptor plays only a minor role in the histamine-induced wheal response in squirrel monkeys and guinea pigs.View full abstractDownload PDF (474K) -
Yutaka Matsuoka, Toshihiko Sugioka, Yasufumi Terawaki, Tsutomu Uruno, ...1993 Volume 63 Issue 1 Pages 101-108
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSCharacteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, β-phenylethylamine (PEA) and β-hydroxyphenylethylamine (OHPEA), were examined. The antinociception induced by PEA derivatives was enhanced by intracisternal injection of norepinephrine or clonidine and attenuated by intracisternal injection of phentolamine or yohimbine, but was not affected by intracisternal injection of prazosin in the mouse hot plate method. PEA derivatives induced a contraction of the rat vas deferens, and this contraction by PEA derivatives was attenuated by the application of phentolamine. The contractions induced by PEA or OHPEA in the reserpinized vas deferens were much smaller than those in the normal one. PEA derivatives inhibited the electrical stimulation-evoked contractions of the vas deferens, and the inhibition by PEA derivatives was reversed by the application of yohimbine. These findings indicate that PEA derivatives may induce the antinociception as a result of stimulating the α2-adrenoceptors. The stimulation of α2-adrenoceptors by PEA derivatives may result from the release of endogenous norepinephrine and/or from direct action on the α2-adrenoceptors.View full abstractDownload PDF (540K) -
Yasuo Etoh, Mizuo Miyazaki, Hiroshi Saitoh, Noboru Toda1993 Volume 63 Issue 1 Pages 109-119
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSBiochemical and pharmacological properties of KRI-1314, a newly synthesized, low molecular weight (M.W.: 690) renin inhibitor, were investigated in vitro and in vivo. The novel amino acid norstatine, which is shorter in chain length than the well-known statine, was incorporated into KRI-1314 as a tetrahedral transition-state analogue for the Leu10-Val11 scissile peptide in the renin substrate. KRI-1314 more strongly inhibited plasma renins from primates than those from dogs, rabbits, guinea pigs and rats. KRI-1314 competitively inhibited highly-purified human renin with a Ki value of 9.9×10-10 M. KRI-1314 strongly inhibited the tissue renin-like activities of various organs from Japanese monkeys, with IC50 values on the order of 10-8 M. KRI-1314 was also very stable in various tissue homogenates from Japanese monkeys. Both intravenous (from 0.25 to 3 mg/kg) and oral (10 and 30 mg/kg) administration of KRI-1314 to anesthetized and conscious sodium-depleted Japanese monkeys, respectively, significantly lowered the blood pressure and plasma renin activity without affecting the heart rate. In Japanese monkeys, KRI-1314 was continuously detected in the plasma up to at least 7 hr after oral administration of 10 and 30 mg/kg. These results demonstrate that KRI-1314 is a highly potent, primate-selective and long-lasting oral renin inhibitor with a blood pressure lowering effect.View full abstractDownload PDF (863K) -
Akira Kanda, Hiroo Hashimoto1993 Volume 63 Issue 1 Pages 121-124
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe acute antihypertensive effects of orally administered semotiadil, a novel calcium antagonist, were compared with those of nifedipine and diltiazem in conscious, unrestrained spontaneously hypertensive rats (SHRs). Semotiadil (10 and 30 mg/kg) produced a dose-dependent hypotension that persisted for 18 hr at 30 mg/kg. Diltiazem (30 and 100 mg/kg) and nifedipine (1 and 3 mg/kg) also exhibited hypotension dose-dependently, but their durations of actions were shorter than that of semotiadil. Semotiadil caused a slight increase in heart rate, while diltiazem and nifedipine caused a bradycardia and a marked tachycardia, respectively. These results suggest that semotiadil has a beneficial property as an anti-hypertensive drug.View full abstractDownload PDF (293K) -
Shigemasa Kinbara, Kaoru Ishizaki, Yoshishige Takeuchi, Norio Miyazawa ...1993 Volume 63 Issue 1 Pages 125-127
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated the effects of tauroursodeoxycholate (UR-906) and ursodeoxycholic acid (UDCA) on α-naphthylisothiocyanate (ANIT)-induced cholestasis in mice. UR-906 and UDCA were given intravenously 2 hr prior to and 2 hr after ANIT (80 mg/kg, p.o.) treatment. The animals were sacrificed 48 hr after ANIT administration, and serum markers of liver injury were examined. UR-906 prevented significant elevations in total bilirubin, bile acids and LDH. Furthermore, this drug reduced significant elevations in ALP and LAP. UDCA also prevented significant elevations in total bilirubin and LAP. These results indicate that UR-906 as well as UDCA has a beneficial effect against ANIT-induced cholestasis in mice.View full abstractDownload PDF (164K) -
Asaki Abe, Hideaki Karaki1993 Volume 63 Issue 1 Pages 129-131
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe phosphatase inhibitor okadaic acid at 100 nM slowly but completely inhibited high K+-induced contraction in the rat aorta (t1/2=118.9 min). High K+-induced contraction was partially inhibited (to 37-65%) by 1 iM forskolin, 100 μM dibutyryl cyclic AMP, 100 nM atrial natriuretic peptide, 1 μM nitroglycerin, 10 nM sodium nitroprusside, 300 pM nicardipine or 100 nM verapamil. The rate of relaxation due to okadaic acid became faster when the contraction was partially inhibited by these compounds. Augmentation of the relaxation was greater with forskolin and dibutyryl cyclic AMP than with the other inhibitors. These results support the suggestion that okadaic acid inhibits phosphatase to augment the phosphorylation due to cyclic AMP-dependent kinase, resulting in smooth muscle relaxation.View full abstractDownload PDF (232K)
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