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Volume 39 (1985)
- Issue 4 Pages 419-
- Issue 3 Pages 285-
- Issue 2 Pages 123-
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Volume 39, Issue 4
Displaying 1-18 of 18 articles from this issue
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Yuko SUZUKI, Hideyo OHSHIKA1985 Volume 39 Issue 4 Pages 419-424
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe present study was carried out to determine the β-receptor subtype responsible for the hypertrophy and dysfunction of parotid glands in rats chronically treated with isoproterenol (ISP). Treatment with dobutamine (DBT), a β1-agonist, (30 mg/kg twice a day for 4 days) produced a significant enlargement of the parotid gland just as in the ISP-treated rats. The effects of secretagogues on amylase release and ISP-induced cyclic AMP accumulation were markedly decreased in the parotid tissue of the treated rats. Co-administration of the β1-antagonists metoprolol and acebutolol clearly inhibited the development of parotid enlargement and its secretory dysfunction induced by ISP or DBT. Procaterol treatment (30 mg/kg, twice a day for 4 days) did not cause any dysfunction or any increase in the gland weights. These results indicate that both hypertrophy and dysfunction of the rat parotid gland, which were observed in chronic treatment with ISP, may result from chronic stimulation of β1-adrenoceptors.View full abstractDownload PDF (483K) -
Shigehiko NARUMI, Yasuo NAGAI, Yoshiaki SAJI, Yuji NAGAWA1985 Volume 39 Issue 4 Pages 425-435
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSSlices of the nucleus accumbens, the terminus of the mesolimbic dopaminergic system and the striatum, the terminus of the nigrostriatal dopaminergic system obtained from rats, were used for analyzing the dopamine releasing effects of TRH and its analog DN-1417 (γ-butyrolactone-γ-carbonyl-L-histidyl-L-prolinamide citrate). (1) Dopamine release: The addition of DN-1417 (5×10-5 M) or TRH (5×10-4 M) stimulated the release of prelabelled [3H]-dopamine (DA) from the superfused nucleus accumbens slices, and 100 or 20 times higher concentrations of each compound stimulated DA release from the striatal slices. The omission of Ca2+ from the superfusion medium or the addition of ouabain (5×10-3 M), a (Na++K+) stimulated adenosine triphosphate (ATP) phosphohydrolase [(Na++K+)-ATPase] inhibitor, almost completely abolished the DN-1417 or TRH-induced DA releasing effect. (2) 45Ca2+ uptake: The addition of DN-1417 (10-4 M) or TRH (10-4 M) stimulated 45Ca2+ uptake into the nucleus accumbens slices in a time-dependent manner from 1 to 5 min at 30°C. On the other hand, both drugs (10-4 M) had no effect on 45Ca2+ uptake into the striatal slices. A Ca2+ ionophore, A-23187 (10-6 M), stimulated 45Ca2+ uptake into slices of the nucleus accumbens and striatum. Ouabain abolished the DN-1417-, TRH- and A-23187-induced effects. (3) Cyclic AMP formation: The addition of DN-1417 (10-4 M) or TRH (10-4 and 10-3 M) accelerated cyclic AMP formation in the nucleus accumbens, but not in the striatal slices. A Ca2+ antagonist, methoxyverapamil (D-600, 10-6 M) almost completely abolished the DN-1417 and TRH-effects. (4) (Na++K+)-ATPase activity: The addition of DN-1417 (10-5 and 10-4 M) or TRH (10-4 M) activated (Na++K+)-ATPase in the P1 fraction (cell debris, nuclei) of the nucleus accumbens, but had little effect on the same activity in the striatum. (5) [3H]-TRH binding: The addition of 10-6 to 10-4 M of DN-1417 and TRH inhibited concentration-dependently [3H]-TRH binding in the nucleus accumbens and striatal slices. Ouabain (5×10-3 M) almost completely abolished [3H]-TRH binding in both types of slices. These results suggest that DN-1417 and TRH activate (Na++K+)-ATPase and stimulate Ca2+ uptake in the presynaptic sites and release DA which stimulates cyclic AMP formation in the postsynaptic sites of the mesolimbic dopaminergic system mainly and causes several central nervous actions.View full abstractDownload PDF (745K) -
Yoko ANIYA, Matao SAKANASHI, Katsuhiko NOGUCHI, Kichihiko MATSUSAKI1985 Volume 39 Issue 4 Pages 437-441
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe biological activity of a Habu (Trimeresurus flavoiridis) venom fraction with drug-metabolizing enzyme inhibitory action was studied. The venom fraction, which was isolated through Sephadex G-100 gel filtration and cation exchange chromatography on Amberlite CG50, caused an increase of vascular permeability and hemorrhage, but these actions were lost after heating at 70°C for 5 min. The fraction showed anticoagulant activity on citrated blood, and this activity remained after heating of the venom. Guinea pig ileum was contracted by treatment with nonheated or heated venom fraction, and these contractions were inhibited with atropine and potentiated with physostigmine. These results suggest that the drug-metabolizing enzyme inhibitor isolated from Habu venom involves the heat stable component with anticoagulant activity and smooth muscle contractile action.View full abstractDownload PDF (525K) -
Yoshiki MIURA, Tsugutaka ITO, Toshiaki KADOKAWA1985 Volume 39 Issue 4 Pages 443-451
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSAn acute animal model with irreversible ischemia in the pons (Pons Ischemic Rat, PIR) was developed by two placed occlusions of the basilar artery. PIR showed decerebrate syndromes. Electroencephalograms (EEGs) in d-tubocurarine-immobilized PIR showed inclusion of obviously higher amplitude slower waves in the cortex but similar θ waves in the hippocampus, as compared with those in intact rats. Spontaneous cortical EEGs in PIR were desynchronized by pinching of hind limbs. From the frequency analysis, it was found that this cortical EEG alterations were composed of the decrease of β2 band relative power and the increase of δ-θ2 bands. Haloperidol, at the dose without effect on EEG in intact rats, dose-relatedly decreased the cortical β2 band in PIR, and the potency was 100 times stronger than that in intact rats. On the other hand, the potency of atropine on the cortical β2 band was almost the same in both preparations. Apomorphine, thyrotropin-releasing hormone (TRH), methamphetamine, physostigmine and amantadine dose-relatedly increased the cortical β2 band in PIR, and these increasing effects, except in the case of physostigmine, were antagonized by the pretreatment of haloperidol. These results suggest that PIR is positioned as an animal model with the moderately lowered consciousness level intensively corresponding to semi coma in patients, and the dopaminergic system plays an important role rather than the cholinergic system in PIR.View full abstractDownload PDF (626K) -
Tsutomu SUZUKI, Yoko KOIKE, Toshio YOSHII, Saizo YANAURA1985 Volume 39 Issue 4 Pages 453-459
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSSex differences in physical dependence on sodium pentobarbital in the rat were studied by the drug-admixed food (DAF) method. With male rats, the concentration of pentobarbital in the food was gradually increased from 2 to 30 mg/g over a period of 50 days. The final level of drug intake was approximately 1.7 g/kg/day. At pentobarbital concentrations of 20 and 22 mg/g of food, sedation and mild muscle relaxation were observed. At the highest drug concentration, 30 mg/g of food, marked muscle relaxation was noted. With female rats, the concentration of pentobarbital in the food was gradually increased from 1 to 16 mg/g over a period of 47 days. The final level of intake was approximately 1.0 mg/kg/day. At drug concentrations of 12 and 14 mg/g, sedation and mild muscle relaxation appeared. At 16 mg/g, female rats showed marked muscle relaxation similar to that of the male rats. To produce severe loss of muscle tone, the male rats required twice as much pentobarbital as the female rats. After substitution of normal food for the pentobarbital-admixed food, various signs of pentobarbital withdrawal occurred in both sexes. These signs included vocalization, irritability, muscle rigidity, tremors and convulsions. Onset of withdrawal was more rapid in the females, and the maximum weight loss was greater, 8.0% compared to 3.8% in the males. Physical dependence on pentobarbital was easily developed in both sexes by the DAF method. There was a marked sex difference in withdrawal which we attribute to sex differences in drug metabolizing enzyme activity.View full abstractDownload PDF (428K) -
Akira YAMAZAKI, Hiroshi KANETO1985 Volume 39 Issue 4 Pages 461-465
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSA single dose of clonidine developed tolerance to its analgesic effect. The tolerance reached its peak acutely on the 2nd day and lasted more than 5 days. Neither the analgesic effect nor the development of tolerance was modified by the pretreatment with naloxone. On the 2nd day, clonidine tolerant animals were also tolerant to morphine, but morphine tolerant animals, after a single dose of morphine on the 1 st day, were not tolerant to clonidine. On the 5th day, however, clonidine tolerant animals were tolerant to morphine, and vice versa. Thus, the interaction between morphine and clonidine was "one-way" on the 2nd day, and cross-tolerance was only demonstrated on the 5th day. With a treatment with clonidine plus naloxone on the 1 st day, the development of cross-tolerance to morphine was completely suppressed on the 2nd day but not on the 5th day. These results confirmed our previous finding that acute and delayed tolerance are different in nature, and the development of tolerance to morphine and clonidine are partially underlaid with a common mechanism which is not mediated by oploid receptors.View full abstractDownload PDF (387K) -
Matsuo KIKUCHI, Sachiko OH-ISHI1985 Volume 39 Issue 4 Pages 467-473
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSRat pleurisy was induced by an intrapleural injection of 1 nmol (0.1 ml) of phorbol myristate acetate (PMA). Accumulation of pleural fluid peaked at a volume of 1 ml at 1 hr, and exudation rate peaked at 30 min when measured by the amount of dye leaked into the pleural cavity during 20 min. Histamine contents decreased in the pleural cell pellets markedly at 30 min and increased in the supernatant fluid simultaneously, reflecting histamine release that occurred in 30 min after PMA. Pretreatment with mepyramine maleate or methysergide 30 min prior to the PMA-injection suppressed the fluid volume significantly. The result indicates that there are involvements of 5-hydroxytryptamine and the H1-receptor of histamine in the vascular permeability increase at the early stage of PMA-pleurisy.View full abstractDownload PDF (450K) -
Takemi YOSHIDA, Toshinori YAMAMOTO, Yoichi MATSUURA, Yukio KUROIWA1985 Volume 39 Issue 4 Pages 475-479
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSDuring the early stages of the carcinogen 2-acetylaminofluorene (2-AAF) feeding, there were marked decreases of hepatic mitochondrial type B monoamine oxidase (MAO) and kynurenine 3-hydroxylase activities in male rats, but not in female rats. The administration of N-hydroxy-2-AAF (N-OH-2-AAF), a proximate carcinogenic metabolite of 2-AAF, to male rats also resulted in the decrease of both enzyme activities. The findings indicate that type B MAO and kynurenine 3-hydroxylase which reside in the outer mitochondrial membranes are susceptible to 2-AAF during the early stages of its hepatocarcinogenesis.View full abstractDownload PDF (370K) -
Yoshito NAKAGAWA, Hajime NAKAHARA, Wan-Pao CHIN, Shoichi IMAI1985 Volume 39 Issue 4 Pages 481-485
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSIn pithed rats two recently-introduced β-blockers, nipradilol and arotinolol, as well as labetalol shifted the pressor dose-response curve for phenylephrine to the right. Labetalol and arotinolol did not modify the pressor dose-response curve for clonidine, while nipradilol induced a definite rightward shift. These results indicate that labetalol and arotinolol are selective α1-blockers, while nipradilol is a non-selective one. In addition, all the three β-blockers produced complex changes in the blood pressure in pithed rats. A fall of the diastolic blood pressure induced by labetalol and nipradilol was preceded by a slight rise, while arotinolol produced a fall at lower doses and a rise at higher ones. The hypotension by labetalol was abolished after propranolol, while the hypertension was suppressed by prazosin, indicating that labetalol has an intrinsic β- and α1-sympathomimetic effect. The hypertension and the hypotension produced by nipradilol and arotinolol persisted even in the presence of propranolol and prazosin or propranolol and yohimbine.View full abstractDownload PDF (329K) -
Hajime NAKAHARA, Mikio NAKAZAWA, Keisuke TAKEDA, Shoichi IMAI1985 Volume 39 Issue 4 Pages 487-492
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSAcute hypotensive effects and the mechanisms of three β-adrenergic blocking drugs with α-blocking activity were studied in comparison with those of prazosin, propranolol and hydralazine in the conscious spontaneously hypertensive rat (SHR). Prazosin lowered the blood pressure dose-dependently and inhibited the pressor response to phenylephrine. Three β-adrenergic blocking drugs with α-blocking activity, labetalol (30 mg/kg), arotinolol (100 mg/kg) and nipradilol (100 mg/kg) also lowered the blood pressure to the same extent as prazosin (0.3 mg/kg), but the inhibition of the pressor response to phenylephrine produced by them was disproportionately slight. Propranolol (100 mg/kg) did not lower the blood pressure. These results suggest that the acute hypotensive effects of three β-adrenergic blocking drugs with α-blocking activity were attributable only partially to the α-adrenergic blocking effect; a mechanism or mechanisms other than the α-adrenergic blocking effect must be invoked to explain the acute hypotensive effect produced by lower doses of these drugs in the conscious SHR.View full abstractDownload PDF (434K) -
Tetsuhiro HISAYAMA, Issei TAKAYANAGI1985 Volume 39 Issue 4 Pages 493-501
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe effect of readmitted Na on the Ca-depletion process in the carbachol-sensitive Ca-store was investigated using thin bundles of the K-depolarized, Na-depleted guinea-pig taenia caecum. To estimate the quantity of stored Ca, the "Ca-load Ca-release" method was employed: To load the store with Ca, 2 mM Ca was added and left (phase A), and then it was removed by washing with 2 mM EGTA-containing solution (phase B); 10-3 M carbachol was then applied (phase C). Instead of glucose, pyruvate was used as a nutrient. Millimolar concentrations of Na inhibited the carbachol-induced contractions when Na was present during phase B. Na present during phase A also reduced the carbachol-induced contraction, but not when Na was treated during phase C. As the period of phase B was prolonged, the carbachol-induced contraction was reduced, which suggests the depletion process of stored Ca resulting from extrusion of Ca from the cell. Na present during phase B accerelated the rate of the Ca-depletion process. Li mimicked Na with regard to the promoting effect on the depletion process, and the effect of Na was not affected by 10-4 M ouabain, suggesting that Na-Ca exchange would not be involved in the effect of Na. These results suggest that Na may be involved in the maintenance of cellular Ca-homeostasis through the stimulation of efflux of Ca from the store to the outside of the cell.View full abstractDownload PDF (737K) -
Masako OKAZAKI, Eiji FURUYA, Takako KASAHARA, Koji SAKAMOTO1985 Volume 39 Issue 4 Pages 503-514
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSPhagocytic activity as a function of the reticuloendothelial system (RES) has been studied in CCl4-induced liver injury by using the carbon clearance test. Liver damage in mice was induced by administration of 20% CCl4 in olive oil (p.o.). After a single administration of CCl4, significant increases in liver/body weight ratio, serum GOT and GPT levels, α, β and γ-globulins and BSP retention, and decreases in serum albumin, an activity of the hepaplastintest and the correct phagocytic activity, α value, were found. After 15 administrations of CCl4 (3 times a week), mild increases in serum GPT level and BSP retention and decreases in the activity of the hepaplastintest and both phagocytic indices, K and α values, were observed. However, zymosan treatment 3 days before sacrifice induced an increase in K value depressed by multiple administrations of CCl4. The depression of carbon uptake by Kupffer cells can be seen by light microscopy after multiple administrations of CCl4 compared with that of saline and olive oil. These findings indicate that the RES phagocytosis is suppressed more strongly in chronic liver injury by 15 CCl4 administrations than in acute injury by a single one, although the biochemical parameters indicating liver injury are shown to have an opposite tendency. A clear correlation between the alteration of RES activity and the degree of liver injury was not noted.View full abstractDownload PDF (1379K) -
Masayuki NIWA, Takashi NOSE, Masakatsu NOZAKI, Kaito TSURUMI, Hajime F ...1985 Volume 39 Issue 4 Pages 515-528
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe effects of butorphanol and its main metabolites, norbutorphanol and hydroxybutorphanol, on the contents of monoamines and their metabolites in various regions of the rat brain were compared with those of morphine and pentazocine using the H PLC-ECD method. The administrations of morphine and pentazocine increased dopamine turnover in the striatum and hypothalamus in a drug dose-dependent manner. The stimulative effects of butorphanol on the dopamine system were weaker than those of morphine and pentazocine, and there were no dose-dependencies in these effects of butorphanol. Butorphanol, morphine and pentazocine increased 5-HT turnover, but there was no drug dose-dependent effect in the case of butorphanol. These differences for the effects of butorphanol from those of morphine and pentazocine seemed to result from the antagonist-agonist property of butorphanol and from a different manner of interaction with the opioid receptor. The effects of butorphanol on the levels of the norepinephrine system were weak. It was considered that the effects of butorphanol on monoamine turnover were produced by the action of butorphanol itself, because norbutorphanol and hydroxybutorphanol showed little change on the level of monoamines and their metabolites.View full abstractDownload PDF (858K) -
Kiyofumi SAIJOH, Hiroshi FUJIWARA, Chikako TANAKA1985 Volume 39 Issue 4 Pages 529-539
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSWe studied the influence of hypoxia on the release of [3H]dopamine ([3H]DA) and [3H] acetylcholine ([3H]ACh), uptake of [3H]DA and [3H]choline and Ca2+-influx in guinea pig striatal slices. Tetrodotoxin (TTX)-sensitive and Ca2+-dependent electrically evoked release of [3H] DA was not affected by hypoxia, while spontaneous release of [3H] DA was rapidly increased. On the other hand, by hypoxia, the evoked [3H]ACh release gradually decreased and was diminished to about 45% 40 min later. Hypoxia suppressed the Vmax of [3H] DA uptake to one third and that of [3H]choline to half of the control values, but with no change in either of the Km values. Hypoxia reduced both the acetylation and the uptake of [3H]choline in slices preliminarily incubated with 3 mM or 25 mM K+ medium. Stimulation-induced Ca2+-influx was slightly suppressed and was 78.1% of the control values even after 40 min exposure to hypoxia. The Ca2+-dependent neurotransmitter release process itself appears to be well preserved against hypoxia as compared with the uptake process. Our findings imply that hypoxia could result in differential alterations of neural activity depending on the specific sensitivity of the presynaptic process of neurotransmission.View full abstractDownload PDF (810K) -
Kazuaki NAITO, Taku NAGAO, Yasutoshi ONO, Minezo OTSUKA, Shoichi HARIG ...1985 Volume 39 Issue 4 Pages 541-549
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSAffinities of denopamine, a new cardiotonic agent, and several β-adrenergic drugs for turkey erythrocyte membranes (TEM) and rat reticulocyte membranes (RRM) which contain homogeneous β1- and β2-receptors, respectively, were studied by receptor binding. The order of potencies of denopamine and several β-adrenergic agonists in displacing 3H-dihydroalprenolol binding (Ki, nM) in TEM was isoproterenol (Iso, 27)>norepinephrine (Nor, 360)>epinephrine (Epi, 860)>dobutamine (DB, 1380)>denopamine (1540)>dopamine (DA, 49500). The order in RRM was Iso (7.3)>Epi (58)>DB (750)>Nor (1090)>denopamine (2300)>DA (26800). In the presence of GTP, competition curves for full agonists like Iso, Epi and Nor shifted to the low affinity side (Ki values increased by 300-500% in TEM and 200-460% in RRM), and the slopes were steepened in both membrane preparations. The Ki value for denopamine increased only in TEM (70%) and that in RRM was not influenced by GTP. This suggests that denopamine has an agonist property at the β1-receptor but not at the β2-receptor and that the intrinsic activity at the β1-receptor of the drug is lower than full agonists. Affinities of DB and DA for TEM were influenced by GTP as well as those for RRM, although the extent of the rightward shift was less than full agonists.View full abstractDownload PDF (699K) -
Meng Kwoon SIM, Mui Eng CHUA1985 Volume 39 Issue 4 Pages 551-553
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThis study investigates the response of the noradrenaline-contracted aorta of normotensive, renal-induced and spontaneously hypertensive rats to acetylcholine (ACh) and histamine. Aortae of the renal-induced hypertensive rats compared to the those of the normotensive rats were hypo-responsive to the two vasodilators, indicating that the sensitivity of the endothelial histamine and acetylcholine receptors is significantly lower. However, with the spontaneously hypertensive rats, the high blood pressure appears to affect only the histamine receptors.View full abstractDownload PDF (224K) -
Taizo KITA, Toshikatsu NAKASHIMA, Yutaka KUROGOCHI1985 Volume 39 Issue 4 Pages 554-557
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSEffects of nicotine on circadian rhythms of ambulatory activity and drinking in male Wistar rats were examined. Nicotine was administered through the drinking water, and the daily doses of nicotine were adjusted to 0.5, 5 and 20 mg/kg/day. The treatment of nicotine induced a dose-dependent increase in ambulatory activity. On the other hand, fluid intake decreased at a dose of 20 mg/kg/day. Although the ambulatory activity and drinking were influenced by a long-term oral administration of nicotine, their circadian patterns, which were characteristic of nocturnal animals, were not altered.View full abstractDownload PDF (274K) -
Shoichi TOMONO, Kinya KURIYAMA1985 Volume 39 Issue 4 Pages 558-561
Published: 1985
Released on J-STAGE: September 15, 2006
JOURNAL FREE ACCESSThe effect of 450191-S, one of the 1H-1, 2, 4-triazolyl benzophenone derivatives and possessing benzodiazepine-like anti-anxiety actions, on the content of various amino acids in the mouse brain was examined in comparison with that of nitrazepam. Among the various amino acids examined, only glycine, aspartic acid and alanine showed a statistically significant decrease following the oral administration of 450191-S. The oral administration of nitrazepam also induced a similar decline in the cerebral contents of glycine and alanine. Furthermore, it was found that the administration of Ro 15-1788, a benzodiazepine antagonist, eliminated the 450191-S-induced decline in the cerebral contents of glycine and aspartic acid. These results indicate that the administration of 450191-S induces the decrease of glycine and aspartic acid, neuroactive amino acids, in the brain, possibly via the activation of benzodiazepine receptors.View full abstractDownload PDF (285K)
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