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Volume 58 (1992)
- Issue 4 Pages 331-
- Issue 3 Pages 201-
- Issue 2 Pages 83-
- Issue 1 Pages 1-
Volume 58, Issue 4
Displaying 1-19 of 19 articles from this issue
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Miwa Misawa, Yoshinori Takahashi, Junzo Kamei, Tomokazu Hosokawa1992 Volume 58 Issue 4 Pages 331-338
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSWe investigated the involvements of sympathetic and nonadrenergic nervous systems in the inhibitory reflex following bronchoconstriction in dogs. Inhalations of a 0.00125% solution of histamine and Ascaris suum antigen (3 mg protein) to the bronchial side induced reflex tracheal constriction following bronchoconstriction. An intra-arterial infusion of 5 μg/min of atropine to the tracheal site changed the reflex tracheal constrictions by histamine and antigen inhalations into tracheal dilatations. The reflex tracheal dilatations were abolished by the combination of intra-arterial propranolol (100 μg) and transections of both the bilateral superior laryngeal nerves and the spinal cord at the C1 level. The reflex tracheal constrictions induced by histamine and antigen inhalations were increased with 100 μg propranolol. Furthermore, the reflex tracheal constrictions were enhanced by the combination of 100 μg propranolol and transection of the spinal cord. These findings indicate that during the constriction of the bronchial smooth muscle, not only a reflex tracheal constriction mechanism but also one of reflex dilatation operates and that the latter reflex response may be mainly mediated by the sympathetic nerves, with partial involvement of the nonadrenergic nerves. This inhibitory reflex may attenuate asthmatic broncho-constriction.View full abstractDownload PDF (422K) -
Effects of Adrenergic Agonists on an Experimental Urinary Incontinence Model in Anesthetized RabbitsHitoshi Kontani, Mikiko Nakagawa, Takeshi Sakai1992 Volume 58 Issue 4 Pages 339-346
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSWe have developed an experimental urinary incontinence model in anesthetized female rabbits, in order to study the effects of alpha adrenergic receptor agonists on it in vivo. Micturition was induced artificially by electrical stimulation of the abdomen of rabbits receiving a continuous infusion of glucose-free. Tyrode''s solution into the urinary bladder. Alpha-1 adrenergic agonists, phenylephrine (1 mg/kg, i.v.) and the newly synthesized agent ST-1059 (1 mg/kg, i.v.) and its prodrug midodrine (10 mg/kg), which was intraduodenally administered, elevated the bladder pressure and arrested micturition induced by electrical stimulation. Prazosin (0.1 mg/kg, i.v.) inhibited these effects of phenylephrine. The effect of an alpha-2 agonist, clonidine (1 mg/kg, i.v), on micturition induced by electrical stimulation was not clearly defined. This study demonstrates that alpha-1 adrenergic agonists can arrest artificially-induced micturition via urethral contraction. This method may be useful for evaluating the effect of a drug on urethral leakage in vivo.View full abstractDownload PDF (395K) -
Hiroshi Kasai, Toshio Kawashima, Shigeki Omura, Yukiyoshi Yanagihara1992 Volume 58 Issue 4 Pages 347-355
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESS-The effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-a]pyrimidin-4-one (AS-35), a newly synthesized compound, on leukotrienes (LTs) antagonistic activities were investigated in vitro and in vivo. In isolated guinea pig preparations, AS-35 antagonized LTC4-, LTD4- and LTE4-induced contractions of the ileum with IC50 values of 8 nM, 4 nM and 3 nM, respectively. In the trachea, the agent also antagonized LTD4- and LTE4-induced contractions with IC50 values of 10 nM and 20 nM, respectively. However, LTC4-induced tracheal contraction in the presence of L-serine borate was not antagonized by AS-35. Histamine-, acetylcholine-, serotonin- and bradykinin-induced contractions of the ileum, carbachol-, prostaglandin D2-, prostaglandin F2α-induced contractions of the trachea and LTE4-induced chemotaxis of rat polymorphonuclear leukocytes were not inhibited by AS-35. As to the in vivo models, AS-35 (i.v.) dose-dependently antagonized bronchoconstriction induced by i.v.-injection of LTC4 and LTD4 in anesthetized guinea pigs, but did not inhibit histamine-induced bronchoconstriction. Oral administration of AS-35 also antagonized LTD4- as well as antigen-induced LT-mediated bronchoconstriction. In addition, LTD4-induced increase in the cutaneous vascular permeability of guinea pig was inhibited by the drug (p.o.). These results indicate that AS-35 is an orally effective, potent and selective peptide LT antagonist.View full abstractDownload PDF (502K) -
Hiroshi Kasai, Yukiyoshi Yanagihara1992 Volume 58 Issue 4 Pages 357-364
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSThe inhibitory effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)-methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-a]pyrimidin-4-one (AS-35), a peptide leukotriene (LT) antagonist, on specific bindings of radiolabeled LTC4 and LTD4 in guinea pig lung membrane were investigated to clarify the mechanism by which this agent inhibited LT-induced physiological responses. Binding assays were performed at 20°C in 50 mM Tris-HCl buffer (pH 7.4) containing 10 mM CaCl2, 10 MM MgCl2 and 10 mM cysteine in the absence (LTD4 binding assay) or presence (LTC4 binding assay) of 80 mM L-serine borate. Scatchard analysis of each LT specific binding indicated a single and high affinity binding site with a Kd of 0.21 ± 0.05 nM and Bmax of 808 ± 71 fmol/mg protein for [3H]-LTD4, and with a Kd of 21.6 ± 3.8 nM and Bmax of 74.9 ± 2.6 pmol/mg protein for [3H]-LTC4. Competition binding studies showed that AS-35 antagonized [3H]-LTD4 specific binding with a Ki value of 92.7 nM. In contrast, AS-35 was 100 times less effective in inhibiting [3H]-LTC4 specific binding, compared with [3H]-LTD4 specific binding. These results indicate that AS-35 interacts directly with peptide LTs receptors, especially the LTD4 specific binding site to produce its pharmacological effects.View full abstractDownload PDF (388K) -
Yoshikazu Hattori, Norio Inomata1992 Volume 58 Issue 4 Pages 365-373
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSUsing a whole cell clamp technique, the blockade of sodium currents (INa) by pilsicainide, a new antiarrhythmic agent, applied either intracellularly or extracellularly, was studied in single myocytes isolated from guinea pig right ventricle. Pilsicainide applied extracellularly inhibited the peak amplitude of INa in concentration (from 10-5 M to 10-4 M) and rate- (from 0.5 Hz to 3.0 Hz) dependent manners. The onset rate of the blockade in INa was almost constant, independent of frequency of stimulus, but higher at high concentration of pilsicainide. The time constant in the recovery phase from INa inactivation remained almost constant (65 to 75 msec) in the range of concentrations used. Similar results were obtained by intracellular application of 10-3 M pilsicainide. Pilsicainide applied intracellularly inhibited INa in a rate-dependent manner. The blocking potency of internally applied pilsicainide almost corresponded to that of external 10-5 M pilsicainide. The onset rate of INa inactivation (from 0.098/pulse to 0.130/pulse) and the recovery time constant (77 msec) was similar to those of external 10-5 M pilsicainide. These results suggest that pilsicainide, irrespective of intra- or extracellular application, shares a common binding site to block INa in cardiac myocytes.View full abstractDownload PDF (465K) -
Akira Fujita, Takashi Takahira, Makoto Hosono, Keita Nakamura1992 Volume 58 Issue 4 Pages 375-381
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSThe efficacy of NKH477, a novel water-soluble forskolin derivative, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital, propranolol or verapamil so that cardiac output had been reduced by about 40-50% of the respective control were all improved by NKH477 (10-100 μg) in a dose-dependent manner. With 100 μg NKH477, almost complete restoration of cardiac performance was attained in the respective cardiac failures. In the combination of NKH477 with ouabain (30 μg), 30 μg of NKH477 completely restored the cardiac function depressed by pentobarbital, associated with a slight but not significant increase in heart rate. No arrhythmias were induced by any of the NKH477 doses used in the experiments. These results suggest that NKH477 should be subjected to clinical trials in the treatment of cardiac failure.View full abstractDownload PDF (350K) -
Mitsutoshi Satoh, Issei Takayanagi1992 Volume 58 Issue 4 Pages 383-389
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSSingle cells were prepared from guinea pig tracheal smooth muscle and used in an experiment on the contraction mechanisms for norepinephrine and a study on the change of α2-adrenoceptors with age. Specific bindings of [3H]p-aminoclonidine to the single cells from the tracheal smooth muscles of 6- and 40-week-old guinea pigs were saturable and analyzed by Scatchard plot. The maximum number of [3H]p-aminoclonidine binding sites was larger in the preparation from 40-week-old guinea pigs than that from 6-week-old animals, while its dissociation constant did not change with age. The amount of prostaglandin F2α released from the single cells was increased by norepinephrine, not affected by phenylephrine, and reduced by an α2-antagonist such as yohimbine. The amount released by norepinephrine was significantly larger in the preparation from 6-week-old guinea pigs than that from 40-week-old animals. These results suggest that the age-related decrease in the potency of norepinephrine is due to reduction in the amount of excitable prostaglandin F2α released by the drug, but not to a change in the total amount of α2-adrenoceptors or the dissociation constant of the drug with respect to these adrenoceptors. Furthermore, α2-adrenoceptors in the tracheal smooth muscle cell play an important role in the release of prostaglandin F2α and the production of contractile responses of these muscles.View full abstractDownload PDF (400K) -
Yoshihide Tatsumi, Tadashi Kodama, Kei Kashima, Seitaro Ohkuma, Kinya ...1992 Volume 58 Issue 4 Pages 391-398
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSTo clarify the role of oxygen radicals in the mucus metabolism of the gastrointestinal tract, the effect of oxygen radicals on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, was investigated using homogenate derived from rat gastric mucosa. The simultaneous addition of both xanthine and xanthine oxidase caused a significant inhibition of the enzyme activity, and this decrease was counteracted by catalase, but not by superoxide dismutase. Hydrogen peroxide also caused a significant decrease in the enzyme activity; and this effect of hydrogen peroxide was counteracted by catalase and dithiothreitol, but not by mannitol, dimethyl sulfoxide and reduced glutathione. The inhibition of glucosamine synthetase activity by oxygen radicals is considered to be caused by the oxidation of sulfhydryl groups of the enzyme molecule. The present results also suggest that oxygen radicals in the gastrointestinal tract may induce the suppression of a protective mechanism of the gastric mucosa by inhibiting glucosamine synthesis activity.View full abstractDownload PDF (393K) -
Akira Ikegami, Akio Ozaki, Hideaki Hara, Takayuki Sukamoto, Akira Yama ...1992 Volume 58 Issue 4 Pages 399-405
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSThe effects of KB-2796, a new diphenylpiperazine calcium antagonist, on the striatal dopaminergic system of rats were investigated in comparison with various calcium antagonists and the dopamine antagonist chlorpromazine. The inhibiting effect of KB-2796 on [3H]spiperone binding to striatal membranes in vitro was weaker than those of chlorpromazine and the other diphenylpiperazine analogues, flunarizine and cinnarizine, and more potent than those of verapamil and nicardipine. Diltiazem and nifedipine were inactive. KB-2796 (30, 100 mg/kg, p.o.) had no effect on Kd and Bmax values of in vitro [3H]spiperone specific binding to striatal membranes obtained from the rat at 36 hr and 7 days after repeated administration for 18 days, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased Bmax values by 47% and 31%, respectively, at 36 hr, but not at 7 days after the final administration. At 1 hr after the single administration, KB-2796 (30, 100 mg/kg, p.o.) had no effect on the content of dopamine and its metabolites in the striatum, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased the level of homovanillic acid. These results indicate that flunarizine may affect dopaminergic neurotransmission by partially blocking dopamine D2 receptors, while KB-2796 has negligible in vivo effect on the dopaminergic system.View full abstractDownload PDF (387K) -
Xiao-Bing Wang, Takeshi Osugi, Shuji Uchida1992 Volume 58 Issue 4 Pages 407-415
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSMuscarinic receptor-mediated elevations in intracellular Ca2+ concentration ([Ca2+]i) in the longitudinal smooth muscle of guinea pig ileum were studied by the use of fura-2 fluorescence. Dose-response analysis indicated a difference in the potencies of carbachol (CCh) to increase [Ca2+]i in the presence and absence of extracellular Ca2+. For the increase in [Ca2+]i due to Ca2+ release from intracellular stores in the absence of extracellular Ca2+, the ED50 value of CCh was 3 × 10-5 M. On the other hand, in the presence of Ca2+, the ED50 value was 2.5 × 10-7 M, indicating that a low concentration of CCh (< 10-7 M) caused influx of extracellular Ca2+ without Ca2+ release. Oxotremorine and pilocarpine induced Ca2+ influx, but were less potent inducers of Ca2+ release. CCh also stimulated the formation of inositol trisphosphates (IP3) with an ED50 value of (4.5 × 10-5 M), which was similar to that for Ca2+ release from intracellular stores. Treatment of the smooth muscle with neomycin (1 mM), a phospholipase C inhibitor, abolished both CCh-induced IP3 formation and Ca2+ release from intracellular stores, but did not affect CCh-induced Ca2+ influx. These results suggest that the pathway for muscarinic stimulation of Ca2+ influx through plasma membranes is different from that for Ca2+ release from intracellular stores, which seems to be coupled with IP3 formation.View full abstractDownload PDF (479K) -
Tsutomu Kobayashi, Rikako Yamauchi, Sakae Murata1992 Volume 58 Issue 4 Pages 417-425
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSBy fura-2 fluorometry, we investigated the direct effects of Ca2+ antagonists including a new benzothiazepine, clentiazem, on the high-K+-evoked increase in the concentration of cytosolic free Ca2+ ([Ca2+]i) in rat cerebral synaptosomes and cultured hippocampal neurons. In both preparations, metal ions inhibited the high-K+-induced increase in [Ca2+]i, in the following order: La3+ > Cd2+ >> Ni2. Although flunarizine and nicardipine inhibited the K+-induced increase in [Ca2+]i in synaptosomes, other Ca2+ antagonists, including clentiazem and nitrendipine, had little effect at 10 μM. In hippocampal neurons, clentiazem inhibited the K+-induced increase in [Ca2+]i at 10 μM, as did flunarizine and nicardipine. However, nifedipine and nitrendipine had little effect in either cultured neurons or in synaptosomes.View full abstractDownload PDF (472K) -
Koichi Nagata, Hiroshi Saito, Norio Matsuki1992 Volume 58 Issue 4 Pages 427-434
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSEffects of neurokinin A (NKA) on sympathetic neurotransmission were studied in rat vas deferens. Although neither prazosin, an α1-adrenoceptor blocker, nor α, β-methylene adenosine triphosphate, a P2-purinoceptor blocker, inhibited the NKA-induced contractions in the epididymal site, high concentration of NKA-induced contractions in the prostatic site were slightly decreased by either of the two blockers. Treatment with guanethidine, which prevents the release of sympathetic transmitters from presynaptic nerve endings, also had no effect on NKA-induced contractions in either site. To investigate the effects of NKA on the adrenergic and purinergic neurotransmission in more detail, we measured transmitter release by using [3H]norepinephrine or [14C]adenosine. Neither spontaneous or nor evoked 3H efflux, indicating NE release, was affected by NKA in either site. NKA enhanced 14C efflux, indicating ATP release, evoked by electrical stimulation in the epididymal site, which may be originated from smooth muscle. In the prostatic site, contractions induced by electrical stimulation were enhanced in spite of no increase in 3H or 14C efflux. These results suggest that: 1) NKA has no effect on presynaptic nerve terminals in both sites, 2) NKA potentiates the effects of neurotransmitters in the prostatic site, and 3) NKA modulates the neurotransmission.View full abstractDownload PDF (436K) -
Tsutomu Suzuki, Yoshinao Shiozaki, Yoshikazu Masukawa, Miwa Misawa, Hi ...1992 Volume 58 Issue 4 Pages 435-442
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSEffects of buprenorphine, U-50, 488H, naltrexone and lithium chloride on cocaine conditioned place preference were examined. Buprenorphine, a mixed opioid agonist-antagonist, blocked the cocaine-induced place preference. Furthermore, the kappa-receptor agonist U-50, 488H and the mu-receptor antagonist naltrexone both antagonized the cocaine preference. U-50, 488H or naltrexone alone induced a place aversion in a dose-dependent manner. However, the cocaine-induced conditioned place preference was not blocked by lithium chloride, although the latter induced a conditioned place aversion, indicating that the antagonism of cocaine-induced place preference by U-50, 488H or naltrexone does not result from a functional antagonism. These results suggest that mu- and kappa-opioid receptors may be involved in cocaine-induced conditioned place preference.View full abstractDownload PDF (393K) -
Toshihiro Shinosaki, Haruhisa Inagaki, Takeshi Nakai, Takeo Yamashita, ...1992 Volume 58 Issue 4 Pages 443-450
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSAn apparent circadian rhythm of plasma uric acid and the effect of handling stress on plasma uric acid level in conscious cebus monkeys were demonstrated. The lowest level of plasma uric acid in the circadian rhythm occurred early in the morning and the highest, before bedtime at night. With experimental handling stress, the plasma uric acid level rose to much more than the maximum level of the circadian rhythm. Stress-induced hyperuricemia could be inhibited without an increase of urinary uric acid excretion by the minor tranquilizer diazepam at doses of more than 1 mg/kg, p.o. On the other hand, benzbromarone at 20 mg/kg, p.o. significantly inhibited the hyperuricemia with a hyperuricosuric effect, while probenecid at 50 mg/kg, p.o. had no effect on either the increased plasma uric acid or urinary uric acid excretion. Accordingly, it is concluded that the plasma uric acid level in conscious cebus monkeys easily fluctuates with experimental conditions and that the animals can be utilized to evaluate the hypouricemic and hyperuricosuric property of benzbromarone-like agents.View full abstractDownload PDF (373K) -
Yasunori Ishii, Tomoyuki Kawai, Minoru Watanabe1992 Volume 58 Issue 4 Pages 451-456
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSCyclopiazonic acid (CPA), a novel specific inhibitor of Ca2+-ATPase in muscle sarcoplasmic reticulum, shortened the Ca2+-dependent after-hyperpolarization (AHP) following a spike in the rat superior cervical ganglion. This inhibitory effect was reversible and dependent on concentrations between 1 and 5 μM. The AHP in the presence of 5 μM CPA was not depressed further by ryanodine, nor was it affected by repetitive stimulation. These results suggest that CPA inhibits the intracellular Ca2+ release, probably due to the depletion of Ca2+ stores induced by inhibition of the ATP-dependent Ca2+ pump.View full abstractDownload PDF (299K) -
Yasuhisa Furuichi, Shoji Takakura, Hisashi Satoh, Jo Mori, Masanobu Ko ...1992 Volume 58 Issue 4 Pages 457-460
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSThe effect of nilvadipine, a dihydropyridine type calcium channel blocker, on local cerebral blood flow (lCBF) was investigated using the autoradiographic iodo[14C]antipyrine technique in rats. In control rats, lCBF in cortical areas and in the superior colliculus and inferior colliculus was higher than that in the hippocampus, septal nucleus, globus pallidus and substantia nigra. Nilvadipine (32 μg/kg, i.v.) increased lCBF in all structures (significantly in 11 of 21 structures) in spite of a 33% reduction in mean arterial blood pressure. These results confirm that nilvadipine has the ability to increase cerebral blood flow.View full abstractDownload PDF (200K) -
Akio Fujimura, Kyo-ichi Ohashi, Akio Ebihara1992 Volume 58 Issue 4 Pages 461-465
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSThe role of adrenal corticoids in the time-dependent changes in the effects of furosemide was examined. Furosemide (30 mg/kg) was given orally to adrenalectomized or sham-operated rats at 12 a.m. or 12 p.m. Urine volume and urinary excretion of sodium and furosemide for 8 hr were significantly greater at 12 a.m. than at 12 p.m. in the sham-operated rats. However, such time-dependent changes in these parameters disappeared in the adrenalectomized animals. These findings indicate that adrenal corticoids are directly or indirectly involved in this event.View full abstractDownload PDF (253K) -
Yasuo Oyama, Lumi Chikahisa, Akemi Hayashi, Toshiko Ueha, Mitsuhiro Sa ...1992 Volume 58 Issue 4 Pages 467-471
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSTo test the possibility that triphenyltin (TPT) increases the intracellular Ca2+ ([Ca2+]i) in neurons as found previously in thymocytes, the effect of TPT on [Ca2+]i was examined in rat cerebellar neurons by a flow-cytometer with fluorescent dyes. TPT at concentrations ranging from 3 × 10-7 M to 1 × 10-5 M dose-depend ently increased the [Ca2+]i. The TPT-induced increase in [Ca2+]i was not attenuated by a Ca2+ channel blocker, suggesting that it was not dependent on voltage-dependent Ca2+ channels. As the concentration of external Ca2+ ([Ca2+]e) increased, TPT produced a more profound increase in the [Ca2+]i. However, the increase in the [Ca2+]i by TPT was observed even in nominally [Ca2+]e-free solution. These results suggest two possibilities. First, TPT may promote Ca2+-influx to the neuron. Secondly, TPT may affect the intracellular Ca-store sites. This study is relevant to the neurotoxicity of organotins because it has become progressively clear that sustained increases in the [Ca2+]i can activate various Ca2+-dependent degradative processes.View full abstractDownload PDF (275K) -
Nagao Suzuki, Yasuo Gomi1992 Volume 58 Issue 4 Pages 473-477
Published: 1992
Released on J-STAGE: May 17, 2006
JOURNAL FREE ACCESSCP-96, 345, a novel non-peptide antagonist of the NK1 receptor, at 10-8-10-6 M decreased the frequency of peristalsis and reduced peristalsis-associated longitudinal muscle contractions in isolated guinea pig ileum. In the presence of 10-6 M CP-96, 345, further addition of 10-6 M atropine blocked the peristalsis. When 10-6 M atropine was first applied, more than half of the preparations developed atropine-resistant peristalsis. CP-96, 345 at 10-6 M blocked the atropine-resistant peristalsis. These results are consistent with the view that substance P is involved in the peristalsis in guinea pig ileum.View full abstractDownload PDF (265K)
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