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Volume 51 (1989)
- Issue 4 Pages 455-
- Issue 3 Pages 309-
- Issue 2 Pages 151-
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Volume 51, Issue 3
Displaying 1-21 of 21 articles from this issue
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Renato GAGGI, Rosaria DE IASIO, Anna Maria GIANNI1989 Volume 51 Issue 3 Pages 309-320
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effects of s.c. administered salmon calcitonin on the biogenic amine neurotransmitters and metabolites were studied in discrete brain sections in order to evaluate the relationships between these central effects and the fall of serum calcium and to investigate the mechanisms of calcitonin-induced behavioral changes. The biogenic amines and metabolites were simultaneously determined by high-performance liquid chromatography with electrochemical detection in tissue samples obtained from rats treated with 10-80 MRC U/kg of the peptide. Some rats were pretreated with calcium lactate to inhibit the calcitonin-induced hypocalcaemia. Most of the effects, consisting of signs of serotonergic system activation, have been observed in the hypothalamus, accounting for some behavioral effects of the peripherally administered salmon calcitonin. It was speculated that the activation of the brain serotonergic system could result from two indirect and separate mechanisms: the first, which would involve enhanced serotonin synthesis, seemed to be facilitated by calcium availability. A second possible mechanism, which would involve enhanced serotonin release from the neurons, seemed to be mediated by the fall of calcium levels in the blood.View full abstractDownload PDF (679K) -
Jong Hwa LEE, George B. FRANK1989 Volume 51 Issue 3 Pages 321-327
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effects of ±ketamine were tested on the excitability of frog sciatic nerves using a sucrose gap apparatus and skeletal muscle fibers using intracellular microelectrodes. When applied extracellularly by perfusion, ketamine depressed the action potential of sciatic nerves in a dose-dependent manner. This depression was partially antagonized by the simultaneous treatment with a small concentration of naloxone. However, when the ketamine was applied intracellularly by placing it in a compartment with a cut end of the nerve, only very small and inconsistent decreases were produced. Ketamine also blocked excitability in skeletal muscle by depressing the sodium conductance (gNa). This also could be partly antagonized by the addition of a small concentration of naloxone to the solution bathing the muscle. These results support previous findings by other workers that ketamine has a stereospecific opioid agonist effect in addition to its other actions.View full abstractDownload PDF (426K) -
Masakatsu TAKAHASHI, Keiko SUGIMACHI, Hiroshi KANETO1989 Volume 51 Issue 3 Pages 329-336
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSTo elucidate the mechanism for the suppression by concurrent footshock (FS) exposure of the development of morphine tolerance, the effect of adrenalectomy and a possible participation of glucocorticoids in the mechanism were examined. The analgesic effect of morphine was potentiated in adrenalectomized (ADX) mice, and further enhancement of the effect was shown by the simultaneous exposure to FS (2 mA, 0.2 Hz, 1 sec duration for 15 min) stress, while no such effects were observed in sham-operated (Sham) animals. Daily morphine treatment developed tolerance in Sham and ADX mice. The combined treatment with FS stress suppressed the development of morphine tolerance in Sham mice, whereas such suppression was abolished by adrenalectomy. The suppression of tolerance development was restored in ADX mice by supplement of prednisolone. In contrast to FS stress which produces analgesia through an opioid receptor, forced swimming stress which exerts analgesia through a non-opioid mechanism did not affect the development of morphine tolerance in both Sham and ADX mice. Thus, an opioid mediated stress, FS, could prevent the development of morphine tolerance, and adrenal glucocorticoids play an essential role in the mechanism.View full abstractDownload PDF (374K) -
Behavioral Analysis of Zopiclone on the Basis of Their Discriminative Stimulus Properties in the RatTsuneyuki YAMAMOTO, Yoshino KUMASAKA, Showa UEKI1989 Volume 51 Issue 3 Pages 337-345
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSZopiclone is a new cyclopyrrolone derivative which exerts pharmacological activities similar to those of benzodiazepines in behavioral and biochemical studies. In order to clarify the discriminative stimulus properties of zopiclone, 8 rats were trained to discriminate the interoceptive stimulus induced by zopiclone (3.2 mg/kg, i.p.) from those of saline. Following discrimination acquisition, administration of zopiclone resulted in drug-appropriate responding with an ED50 of 1.3 (1.0-1.8) mg/kg. The zopiclone discriminative stimulus generalized to the benzodiazepines diazepam (1.8 mg/kg), nitrazepam (10 mg/kg) and alprazolam (10 mg/ kg). A non-benzodiazepine, suriclone, at 3.2 mg/kg, generalized to the zopiclone stimulus in 5 out of 7 rats, but meprobamate, hydroxyzine, tracazolate and muscimol did not. The benzodiazepine antagonist Ro 15-1788 (1 mg/kg) completely blocked zopiclone stimulus. In contrast, however, bicuculline and pentetrazol failed to antagonize it. The serotonin antagonist cinanserin and ritanserin neither generalized to the zopiclone stimulus nor did they exhibit antagonism. These results suggest that the zopiclone discriminative stimulus is mediated by binding to benzodiazepine receptors and appears not to be related to GABAergic or serotonergic system.View full abstractDownload PDF (512K) -
Kazutoshi YANAGIBASHI, Yuji OHNO, Noboru NAKAMICHI, Takashi MATSUI, Ke ...1989 Volume 51 Issue 3 Pages 347-355
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSTo provide a possible role of peripheral type benzodiazepine receptors in the regulation of glucocorticoid biosynthesis. We have examined the effect of diazepam on the corticoidogenic response to dibutyryl cyclic AMP in isolated bovine adrenal fasciculata cells. Diazepam alone (up to 100 μM) had no effect on the corticoidogenesis. Diazepam caused a dose-dependent potentiation of dibutyryl cyclic AMP-induced corticoidogenesis. However, diazepam had no effect on the corticoidogenic response to ACTH and a high concentration of KCI. The potentiating effect by diazepam was clearly detected after 90 min-incubation, and it was blocked by YM-684 (diazepam antagonist) and ML-236B (cholesterol de novo synthesis inhibitor). Diazepam caused no significant decrease of intracellular content of cholesteryl esters during the corticoidogenic response to dibutyryl cyclic AMP. When the cells were incubated in the presence of (+)-PN200-110, a potent voltage-dependent Ca channel inhibitor, the potentiating effect by diazepam was not affected in spite of a significant inhibition of dibutyryl cyclic AMP-induced corticoidogenesis. These results indicate that the potentiating effect of diazepam on dibutyryl cyclic AMP-induced corticoidogenesis is due in part to the activation of the intracellular cholesterol supply system (cholesterol de novo synthesis) without any change of voltage-dependent Ca channels.View full abstractDownload PDF (411K) -
Shinji SATOH, Takashi FUJIWARA, Eiichiro Nishiye, Kotoko SUMIMOTO, Tak ...1989 Volume 51 Issue 3 Pages 357-368
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effects of a newly synthesized water soluble and light resistant nitrocompound, E-4701, on the electrical and mechanical properties of smooth muscle cells of rabbit mesenteric and coronary arteries were investigated. In the endothelium-denuded rabbit mesenteric artery, E-4701 relaxed the tissue pre-contracted by noradrenaline (IC50=40μM) to a greater extent than that contracted by high K, but to a lesser extent than that contracted by acetylcholine (ACh) or high K in endothelium-denuded rabbit coronary artery (the IC50 was 20 nM or 60 nM, respectively). Nitroglycerin showed much the same relaxing action on the above tissue (IC50 for the ACh or K-induced contraction was 20 nM or 65 nM, respectively). Relaxing actions of E-4701 or nitroglycerin were prevented by 10 μM methylene blue. In muscle cells of the porcine coronary artery, E-4701 or nitroglycerin inhibited the Ca-transient provoked by ACh, as examined using fura-2. Both drugs had no effect on the Ca-induced contraction in skinned muscle strips. ACh produced a transient hyperpolarization with subsequent depolarization, but in the endothelium-denuded tissues, ACh only depolarized the membrane. E4701 inhibited the ACh-induced depolarization, but nitroglycerin did not. We concluded from our observations that E-4701, has the typical characteristics of a nitrocompound with an inhibitory action on the agonist-induced membrane depolarization.View full abstractDownload PDF (688K) -
Kohei SAWAKI, Mitsuru KAWAGUCHI1989 Volume 51 Issue 3 Pages 369-376
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe relationships between the convulsions induced by the local anesthetic procaine and monoamines in the spinal cord were investigated in rats. The levels of dopamine (DA) and serotonin (5-HT) in the spinal cord were timedependently increased after procaine (170 mg/kg, i.p.), which induced clonic convulsions, but the level of norepinephrine (NE) was unchanged. The rats that died during convulsions had a marked increase in DA. Phenobarbital (25 mg/kg, s.c.) produced both depletion of DA and elevation of 5-HT in the spinal cord and completely protected rats against convulsions. A 5-HT precursor, 5-hydroxytryptophan (5-HTP; 20-80 mg/kg, i.p.), suppressed the convulsions in a dosedependent manner as shown by a decrease in the incidence and a prolongation of the latency, but a DA precursor, 3, 4-dihydroxyphenylalanine (L-DOPA; 20-80 mg/kg, i.p.), markedly shortened the latency. Furthermore, the effect of L-DOPA on the convulsions was inhibited by the combination of 5-HTP. α-Methyl-p-tyrosine (20-80 mg/kg, i.p.) or DL-p-chlorophenylalanine (20-80 mg/kg, i.p.), an inhibitor of NE and DA or 5-HT biosynthesis, had a slight effect on the convulsions. These results suggest that procaine causes significant elevations of rat spinal DA and 5-HT in the convulsive process and suggest that dopaminergic and serotonergic neurons may be associated with procaine-induced convulsions.View full abstractDownload PDF (371K) -
Yukio UMEDA, Mikio ARISAWA1989 Volume 51 Issue 3 Pages 377-384
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSReceptors for calcitonin gene-related peptide (CGRP) in the lung membranes of guinea pig were characterized by using a millititer plate precoated with polyethylenimine. Specific binding of 125I-CGRP was time-dependent, rapid, and reversible, and the binding increased linearly with increasing concentrations of membrane protein. Scatchard analysis revealed two classes of CGRP binding sites: high affinity sites with a KD value of 7.17×10-11 M and a Bmax of 364 fmol/mg protein and low affinity sites with a KD value of 1.7×10-8 M and a Bmax of 39594 fmol/mg protein. Furthermore, the specific binding of 125I-CGRP was dissociated in the presence of GTP or Gpp(NH)p, suggesting that CGRP receptors in guinea pig lung membranes were coupled to the guanine nucleotide regulatory protein. Scatchard analysis of CGRP binding in the presence of GTP revealed selective inhibition of the binding to high affinity binding sites. Unlabeled CGRP displaced the binding of 125I-CGRP to guinea pig lung membranes with an IC50 value of 3.1×10-10 M. In contrast, salmon calcitonin and human calcitonin displaced the binding at 600-fold higher concentrations. We suggest that both low and high affinity binding sites for CGRP exist in the lung membranes of the guinea pig, and the high affinity binding sites for CGRP may be coupled to GTP binding regulatory protein.View full abstractDownload PDF (357K) -
Hiromichi TSURU, Sumiko NEGITA1989 Volume 51 Issue 3 Pages 385-395
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSA study was made on the characteristics of β-adrenoceptors in the isolated canine facial, portal and saphenous veins. Ring segments of the facial and saphenous veins and longitudinal strips of the portal vein were suspended in tissue baths containing Krebs solution oxygenated and maintained at 37°C. They were moderately contracted with prostaglandin F2α before examining their relaxation responses. The facial and saphenous veins fully relaxed to isoproterenol, while the aortal vein relaxed to a small extent (20% of maximum relaxation) even in the presence of an α-adrenoceptor blockade. In contrast, both forskolin, a direct activator of adenylate cyclase, and membrane-permeable dibutyryl cyclic AMP similarly relaxed all the veins studied. Thus, the reduction of coupling between β-adrenoceptors and the adenylate cyclase system may be involved in the decreased responsiveness of the portal vein to β-adrenoceptor agonists. In addition, analyses of β-adrenoceptor agonism and antagonism, using selective (β1: T-1583, β2: procaterol) and non-selective (isoproterenol) agonists as well as selective (β1: atenolol, β2: IC1 118, 551) and non-selective (propranolol) antagonists, confirmed that beta;-adrenoceptors in the canine facial vein are not homogeneous, with the β1-subtype predominating over the β2-subtype, and that the canine saphenous vein has a homogeneous population of the β2-subtype, as reported in the other species.View full abstractDownload PDF (591K) -
Ichiro KIMURA, Koji SAITO, Eijiro OZAWA1989 Volume 51 Issue 3 Pages 397-401
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSTo determine the true survival of an exogenous substance in the circulation, it is requisite to assess that of the intact molecules. We studied the survival of chicken transferrin (Tf) in murine circulating blood after i.v. injection. With the aid of polyacrylamide-gel isoelectric focusing, direct immunofixation and densitometry, degradation products of chicken Tfs were found, and the disappearance rate of intact molecules was rather higher than that obtained by the single radial immunodiffusion method. These results strongly suggest that the degradation products must be taken into consideration in studies on the clearance of proteinous substances.View full abstractDownload PDF (248K) -
Ikuko KIMURA, Leonora Rivera PANCHO, Yukiko ISOI, Masayasu KIMURA1989 Volume 51 Issue 3 Pages 403-410
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSWe investigated the influence of the diabetic state on the contractile response of longitudinal segments of isolated mesenteric vein to prostanoids and leukotriene (LT), and the contribution of the vascular endothelium to modulation of the contractile response was determined. The normal mesenteric vein and deendothelialized veins of normal (ddY), diabetic KK-CAy and streptozotocin ddY mice (150 mg/kg, i.v., 6 weeks) were used. In the diabetic state, the contractions produced by noradrendline (60 μM), high K+ solution (143.4 mM), and the thromboxane A2 analogue U-4661 9 (29 nM-29 mM) were not affected, and LTD4 (0.1 nM-1 μM)-induced contraction was suppressed. Contractions induced by prostaglandin (PG) E2 (0.2 μM-2 mM), PGF2α (0.3 μM-0.3 mM) and the prostacyclin derivatives PGI2-Na (10-100 μM) and TRK-100 (0.2 μM-2mM) were significantly enhanced in the presence of an intact vascular endothelium, but not in de-endothelialized segments. The increase in PGF2α (0.28 mM) contractions was dependent on age (correlation coefficient r=0.36, significant difference, P<0.05) and blood glucose (r=0.88, significant difference, P<0.01), but was independent of obesity. The contractile response to PGD2 (0.3-0.9 mM) was enhanced in both intact and de-endothelialized segments. These results indicate that the diabetic state affects prostanoid responses in an endothelium-dependent manner, except for the PGD2 response, which is independent of the endothelium.View full abstractDownload PDF (449K) -
Morihide HIBI, Ken-ichi SHIKADA, Takehisa IWAMA, AKIKO YAMAMOTO, Mitsu ...1989 Volume 51 Issue 3 Pages 411-419
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSWe have investigated the effect of a newly synthesized compound NZ107, 4-bromo-5-(3-ethoxy-4 methoxybenzylamino)-3(2H)-pyridazinone, on bronchoconstriction induced by slow reacting substance of anaphylaxis (SRS-A) in the guinea pig. Orally administered NZ-107 (10 mg/kg, 2 hr) inhibited antigeninduced SRS-A-mediated bronchoconstriction in sensitized guinea pigs. NZ-107 (2 mg/kg, i.v., 1 min) prevented the antigen-induced response about as well as the SRS-A antagonist FPL-5571 2 and rapidly reversed it. This rapid reversal by NZ107 but not FPL-55712 also appeared with the leukotriene (LT) D4-induced contraction of the isolated trachea. NZ-107 more selectively inhibited the LTD4 response than those of histamine, acetylcholine and KCI. Compared to FPL-5571 2, NZ-107 was one-fifteenth less potent in inhibiting the LTD4 response, but two-fold more potent in inhibiting the LTD4 response. NZ-107 inhibited the LTD4 response of the trachea 10-fold more potently than that of the ileum (-log IC50: trachea 5.61, ileum 4.56). The combination of NZ-107 (1 μM) with the β-agonist isoproterenol had no synergistic effect on the LTD4 response, but those of theophylline and papaverine had large effects. From these results, NZ-107 is a selective inhibitor of the SRS-A response and may be useful in the therapy of bronchial asthma and other diseases in which the LTs are thought to be involved.View full abstractDownload PDF (473K) -
Jun YAMADA, Yumi SUGIMOTO, Kazuyoshi HORISAKA1989 Volume 51 Issue 3 Pages 421-424
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe involvement of the 5-HT1A receptor in the 5-HT syndrome (head weaving and hindlimb abduction) induced in DBA mice by tryptamine was investigated. Methysergide, (-)propranolol and spiperone suppressed both the head weaving and hindlimb abduction induced by tryptamine. However, ketanserin and ICS 205-930 did not affect them. Haloperidol induced small decreases in the head weaving, but had no effect on the hindlimb abduction. These results indicate that the 5-HT syndrome induced by tryptamine in mice is mediated by the 5-HT1A receptor. Therefore, 5-HT syndrome may also be associated with the 5-HT1A receptor in mice, as it is in rats.View full abstractDownload PDF (236K) -
Shogo TOKUYAMA, Masakatsu TAKAHASHI, Hiroshi KANETO1989 Volume 51 Issue 3 Pages 425-427
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSβ-Carboline-3-carboxylic acid ethyl ester (β-CCE) dose-dependently potentiated psychological-stress induced analgesia (PSY-SIA), and the effect was reversed by diazepam. Concurrent exposure to PSY stress or concomitant treatment with β-CCE blocked the development of analgesic tolerance to morphine; the effect of PSY stress was antagonized by diazepam, and that of β-CCE was reversed by Ro 15-1788. These results suggest that psychological factors which are mediated through benzodiazepine receptors are involved in the mechanism for blocking the development of analgesic tolerance to morphine by PSY stress.View full abstractDownload PDF (150K) -
Yoshiki IWABUCHI, Chihiro AOKI, Taizo MASUHARA1989 Volume 51 Issue 3 Pages 428-431
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effects of substance P, neurokinin A, physalamine, and eledoisin on the secretion of fluid and glycoproteins from the submandibular glands of various rodents were investigated. Following i.v. injection of each peptide at a dose of 20 μg/kg, the major glycoprotein species secreted from rats and guinea pigs were shown to be electrophoretically identical with those found in the acini. However, saliva was not elicited from the mice and hamsters. These results suggest that in both rats and guinea pigs, tachykinins act on the acinar cells of the submandibular gland only.View full abstractDownload PDF (211K) -
Junzhi WANG, Hitoshi ITO, Keishiro SHIMURA1989 Volume 51 Issue 3 Pages 432-434
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESS-Effects of Astragalus polysaccharide (APS) and Radix hedysari polysaccharide (RHPS) on the third component of complement (C3) cleavage production of macrophages in ICR mouse were investigated by the immunofluorescent method. By two hours after intraperitoneal injection of 500 mg/kg of APS or RHPS, there was an obvious increase in the deposition of C3 on peritoneal macrophages. When APS or RHPS was injected 5 times (1 time/day), the proportion of C3 positive macrophages was more than that of 1 -time injection. At the same time, the number of peritoneal macrophages also increased. Since C3 cleavage product occurred with the activation of C3, the results suggest that the immunopotentiating action of APS and RHPS may be related to the activity of mouse complement C3.View full abstractDownload PDF (173K) -
Toshihiro OKAMOTO, Kazuyoshi KURAHASHI, Motohatsu FUJIWARA, Hiroshi OK ...1989 Volume 51 Issue 3 Pages 435-437
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSEffects of nicotine on the delayed gastric contraction due to vagal afferent stimulation were studied. Cats were pretreated with phentolamine (2 mg/kg, i.v.) and propranolol (1 mg/kg, i.v.). The delayed contraction was inhibited by nicotine (100 to 2000 μg/kg, i.v.) in a dose-dependent manner. The inhibition of the delayed contraction by nicotine was blocked by hexamethonium (20 mg/kg, i.v.). The results suggested that nicotine inhibits the delayed contraction by activation of hexamethonium-sensitive inhibitory neurons in the vagal pathway to the stomach.View full abstractDownload PDF (160K) -
Kimihiro YAMASHITA, Yasufumi KATAOKA, Akira MIYAZAKI, Kazuhiko SHIBATA ...1989 Volume 51 Issue 3 Pages 438-442
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe present study was designed to elucidate the brain site of the anticonflict action of zopiclone (ZOP), a cyclopyrrolone derivative, using the rat conflict procedure. ZOP at 10 μg/μl, bilaterally injected into the mammillary body (MB), produced a significant increase in the punished responses, with no change in the unpunished responses. There were no significant changes in these responses when ZOP was injected into the central amygdala, frontal cortex or dorsal hippocampus. Attention should be given to the possibility that the MB is the site of the anticonflict action of ZOP.View full abstractDownload PDF (257K) -
Kouhei YAZAWA, Chao-Hsiung WANG, Yoshimi MARUOKA, Terumi NAKAJIMA, Hir ...1989 Volume 51 Issue 3 Pages 443-445
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe contents of catecholamines and their metabolites were measured in the adrenals of 3 groups of suncus. The first group was naive housed suncus; the second, suncus with stress-loading; and the third, wild ones. There were no significant differences in dopamine, norepinephrine and normetanephrine levels among the control, stress and wild groups. The content of epinephrine, however, decreased in the stress and wild group to 57% and 18%, respectively. These results suggest that housed suncus can easily react to stressful circumstances.View full abstractDownload PDF (151K) -
Miwa MISAWA, Toshihiko KAWAMURA, Kiyoteru TAKENOUCHI1989 Volume 51 Issue 3 Pages 446-449
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSWe attempted to develop a non immunologically induced asthma model using the calcium ionophore A23187. Inhalation of A23187 (0.001-0.005%) for 5 min in male Hartley guinea pigs caused a marked bronchoconstriction in a dosedependent manner with negligible effect on systemic blood pressure. The A231 87induced bronchoconstriction was strongly inhibited by chlorpheniramine and FPL55712. These results indicate that an asthma-like bronchoconstriction was induced by inhalation of A23187 in guinea pigs, and the main chemical mediators involved in this response would be histamine and peptidoleukotrienes.View full abstractDownload PDF (207K) -
Akira SAKAI, Toshimitsu HORI, Toshiaki OKUDA, Tetsunori MATSUBARA, Kat ...1989 Volume 51 Issue 3 Pages 450-454
Published: 1989
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSTRK-100 (0.03, 0.1 and 0.3 mg/kg, p.o.), a chemically stable analogue of prostacyclin, dose-dependently prevented blood coagulation and glomerular fibrin deposition which were enhanced by 4 hr infusion of endotoxin (100 mg/kg) in rats. In addition, TRK-100 suppressed the generation of endotoxin-induced tissue thromboplastin like activity in cultured human endothelial cells.View full abstractDownload PDF (260K)
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