• Archives of Pharmacal Research
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• v.18 no.2
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• pp.121-128
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• 1995

The role of nitric oxide (NO) in non-adrenegic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the dorsal part of the fuinea-pig gastric fundus. In the presence of atropine and guanethidine, a low frequency-dependent relaxsations which were not affected by adrenergic and cholinergic blockage but abolished by tetrodotoxin. $N^G$-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stiumulations but not the relaxations to exogenous nitric oxide. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer, D-arginine. Exgenous administration of No caused concentration -dependent relaxations which showed a similarity to those obtained with electrical simultaion. Hemoglobin, a NOscavenger, abolished the NO-induced relaxations and also markedly reduced those induced by electrical simultaion. The inhibitory effect os hemoglobin was similar to that of L-NNA. Application of ATP caused weak relaxations compared with those to electrical stimultaion, which were unaffected by L-NNA. Exogenously applied vasoactive intestinal polypeptide (VIP) induced concentration-dependent relaxation which was not affected by L-NNA. These results suggest that NO is produced and released mainly as a neurotransmitter from enteric neurons during NANC relaxation induced by low frequencies and short trains of electrical simulation and has a main role in NANC neurotransmission at relaxation induced by these electrical simultaions in the guinea-pig gastric fundus.

• The Korean Journal of Physiology
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• v.25 no.2
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• pp.133-146
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• 1991

In order to elucidate systematically the effects of serotonin on gastric motility of guinea-pig, the contractile and electrical responses to serotonin were recorded using four kinds of muscle strips prepared from antral circular, antral longitudinal, fundic circular, and fundic longitudinal muscles. Experiments were performed using various methods including isometric contraction recording, transmural electrical field stimulation, junction potential recording, intracellular microelectrode technique, and partition stimulation method. The results were as follows: 1) The effect of serotonin on spontaneous contractions was inhibitory in the circular muscle strips of the antrum and fundus, while it was excitatory in the longitudinal muscle strips of the antrum and fundus. Serotonin changed mainly phasic contractions of both the circular and longitudinal muscle strips in the antrum, while it changed mainly tonic contractions of both the circular and longitudinal muscle strips in the fundus. 2) On the contractions induced by transmural nerve stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum, but it increased them in the other three groups of muscle strips(antral longitudinal, fundic circular, and fundic longitudinal). 3) On the contractions induced by direct muscle stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum and fundus. 4) In the fundic circular muscle strips serotonin potentiated excitatory junction potentials (EJPs), and in the antral circular muscle strips it evoked EJPs after inhibitory junction potentials(IJPS). 5) In the antral circular muscle strips serotonin did not affect the slow wave even at the disappearance of spontaneous contractions. On the contrary it increased the amplitude of the slow wave, when the spike component was potentiated and the second component was inhibited. 6) In the antral circular muscle strips the membrane potential was slightly hyperpolarized, but the membrane resistance was not changed. From the above results following conclusions could be made. 1) Serotonin inhibits spontaneous contractions of the circular muscle layer and it increases those of the longitudinal one, irrespective of the gastric region. 2) In the guinea-pig stomach there exists a serotoninergic facilitatory neuromodulation system which exerts its effect on cholinergically mediated contraction. 3) The excitation-contraction decoupling was observed in the effect of serotonin.

• YAKHAK HOEJI
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• v.39 no.5
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• pp.471-479
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• 1995

The recombinant human epidermal growth factor(DWP 401) was investigated on the pharrnacological actions. DWP 401 had no effects on the hexobarbital-induced sleeping time, locomotor activity, rotarod test, body temperature, analgesic action and anticonvulsant action in mice. It also had no influences on the isolated tracheal muscle and ileum of guinea-pig, isolated uterus and fundus strip of rats. Slight hypotensive action with effect on respiration was revealed at a dose of 8 g/kg i.v. of DWP 401 in rabbits. DWP 401 exhibited a weak inhibitory action of glucose tolerance in normal rats, significantly lowered the blood glucose contents in adrenalectomized rats at .a concentration of 160 g,/kg, and produced a significant inhibitory effect on leucocyte migration in CMC-pouch of rats at a concentration of 32 g/rat. Furthermore, DWP 401 showed a significant decrease on gastric juice volume and acidity. However. DWP 401 had no intestinal propulsion rate and influence on urine excretion.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.224-230
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• 2001

DKY is an oriental drug preparation composed of 17 natural products and is known to have antihyperglycemic action at 100 mg/kg po in animal tests. The general pharmacological properties of DKY preparation were investigate in mice, rats, guinea pigs and rabbits. This preparation did neither show any effects on central nervous system, nor effects on algesia, nor epilepsia at the large doses of 3000 mg/kg po in mice or rats. However, the preparation showed hypothermic action at the doses of 330 and 1000 mg/kg po. In the guinea pig ileum, rat fundus strip and estrogenized rat uterus, DKY did not influence their tension at a concentration of 3$\times$10$^{-3}$ g/ml, and the spasmogenic actions produced by histamine, ACh and 5-HT were not blocked in the presence of DKY at 3$\times$10$^{-3}$ g/ml. The blood pressure and respiration were not considerably influenced at 10 mg/kg iv of DKY in rabbits. It did not influence the intestinal propulsion of mice and the normal gastric secretion of rats. These results may suggest that DKY preparation have little effects on central nervous, autonomic and gastrointestimal systems, except hypothermic action.

• Korean Journal of Pharmacognosy
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• v.20 no.3
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• pp.188-195
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• 1989

Hyangsayangwee-Tang, a combined preparation of crude drugs, which has been used for stomach and intestinal disorder, was examined for anti-spasmodic, anti-ulcerative and anti-emetive effects. Spontaneous motility of isolated ileum was strongly suppressed and inhibitory effects against contraction of isolated ileum induced by acetylcholine and barium chloride were shown in mice. And, contraction of isolated guinea-pig ileum by histamine was inhibited. In rats fundus preparations, Hyangsayangwee-Tang elicited strong relaxation and had antagonist effects against the spasm induced by acetylcholine and barium chloride. A significant inhibitory effect on the intestinal propulsion of barium sulfate in mice was shown. In pylorus-ligated rats, Hyangsangwee-Tang inhibited gastric secretion and showed a strong anti-peptic activity. Protective effects against gastric ulceration induced by pyloric ligation, water-immersion stress, histamine and aspirin were significantly recognized in mice and rats. Hyangsayangwee-Tang decreased cupric sulfate-induced vomitting in frogs.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.154-161
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• 1996

General pharmacological properties of LB-00014, an erythropoietin which was produced by recombinant DNA technique in Biotech Research Institute, LG Chemical Ltd. were examined. The administration of LB-00014 (60, 600, 6000 IU/kg, iv) in mice had no effect in general behavior and central nervous system, and no influences on normal body temperature, writhing syndromes induced by 0.7% acetic acid solution and chemoshock produced by strychnine and pentetrazole solution. LB-00014 (60, 600, 6000 IU/kg, iv) given to anesthetized rabbits showed no effect on blood pressure of carotid artery and respiration rates, and it did not influence the responses produced by injection of acetylcholine or epinephme. The administration of LB-00014 (601, 600, 6000 IU/kg, iv) in rats had no effect on the plasma prothrombin time, activated partial thromboplastin time and hemolytic action. The platelet aggregation induced by collagen in human plasma was not influenced by LB-00014 (10, 100, 1000 lU/kg, iv). It showed no direct effect at 100 and 1000IU/m1 in isolated stomach fundus and uterus of rats and ileum of guinea-pig, and it also had no inhibition of contraction produced by acetylcholine, oxytocin, serotonin and histamine in the above-mentioned preparations. It did not influence gastric secretion, pH and acid output at 6000 IU/kg, iv in rats, but showed a significant increase in intestinal propulsion of mice at 6000 IU/kg, iv. Its administration (60, 600, 6000 lU/kg, iv) caused no effect on urine and electrolyte excretion in rats. These results indicate that LB-00014 does not exsert any of serious pharmacological effects.

• The Korean Journal of Physiology
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• v.21 no.2
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• pp.225-239
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• 1987

The effects of adenosine on the mechanical contractions and electrical activities were investigated in guinea-pig stomach. Spontaneous contractions of the antral region were recorded with force transducer, and the phasic contractions of fundic region were induced by electrical field stimulation. Electrical responses of smocth muscle cells were recored using glass capillary microelectrodes filled with 3M-KCl. Field stimulation was applied transmurally by using a pair of platinum wire (0.5 mm in diameter) placed on both sides of tissue. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows. 1) Adenosine suppressed the spontaneous contractions of antrum in a dose-dependent manner. 2) The inhibitory effect on antral spontaneous contractions was not influenced by the administration of guanethidine $(5{\times}10^{-6}\;M)$ and atropine $10^{-6}\;M$, or in the presence of dipyridamole $10^{-7}\;M$. 3) The phasic contractions of fundus induced by electrical field stimulation, which disappeared rapidly by the addition of tetrodotoxin $(3{\times}10^{-7}\;M)$, were potentiated by adenosine in the presence of guanethidine. 4) Adenosine decreased the amplitude and the maximum rate of rise of slow waves, and the increased amplitude and rate of rise evoked in the high calcium solution or in the presence of TEA were decreased by adenosine. 5) The non-adrenergic, non-cholinergic inhibitory junction potential (IJP) was inhibited by adenosine in the antral region, while the excitatory junction potential (EJP) in the fundic region was potentiated. From the above results, the following conclusions could be made. 1) Adenosine suppresses the spontaneous contractions of antrum strip by the decrease in amplitude and rate of rise of slow waves. 2) The release of neurotransmitter(s) from non-adrenergic, non-cholinergic nerve terminals is inhibited by adenosine.

• The Korean Journal of Physiology
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• v.23 no.2
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• pp.277-289
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• 1989

The effects of noradrenaline on the contractile and electrical activities were investigated using the circular muscle strips with intact mucosa prepared from the antrum and fundus of guinea-pig stomach. Electrical responses of circular muscle cells were recorded using glass capillary microelectrodes filled with 3 M KCI. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2\;and\;kept\;at\;35^{\circ}C$. The results obtained were as follows: 1) The spontaneous contractions recorded from the antral and fundic circular muscle strips with intact mucosa were suppressed dose-dependently by the application of noradrenaline, whereas those recorded from the mucosa-free strips were potentiated in a dose-dependent manner. 2) The inhibitory influences on the contractile activities in the normal intact strips were developed via both ${\alpha}-adrenoceptors\;and\;{\beta}-adrenoceptors$, while the excitatory influences in the mucosa-free strips resulted from the strong excitatory effect via ${\alpha}-adrenoceptors$ and the weak inhibitory effect via ${\beta}-adrenoceptors$. 3) Noradrenaline produced hyperpolarization of membrane potential, and increased the amplitude and the maximum rate of rise of slow waves in the mucosa-free strips of antral and fundic circular muscle. 4) Apamin blocked the appearance of the component of initial suppression of spontaneous phasic contractions observed in the mucosa-free strips of antral circular muscle after the application of noradrenaline. 5) The inhibitory influences on the contractile activities in the normal strips with intact mucosa remained unaffected even in the strip with separate mucosa, in which mucosa and muscle layer were mechanically disconnected . From the above results, following conclusions could be made. (1) There are no regional differences between the effects of noradrenaline on the antral circular muscle and those on the fundic circular muscle. (2) Excitatory responses to noradrenaline observed in the mucosa-free strip result from the dominant ${\alpha}-excitatory$ and tile weak ${\beta}-inhibitory$ action of noradrenaline. (3) Inhibitory responses to noradrenaline in the normal strips with intact mucosa develop via both ${\alpha}-inhibitory\;and\;{\beta}-inhibitory$ actions.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.106-106
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• 1995

A polysaccharide, G009, isolated from Ganoderma lucidum IY009 subjected to investigating on general pharmacology. This material at the large oral doses of 1000 and 2000mg/kg in mice did neither exhibit any abnormal behaviors nor effects on central nervous system. It also had no influences on hexobarbital-induced sleeping time, rotarod test and spontaneous activity test at each oral dose of 1000mg/kg in mice. No effects on the body temperature and on acetic acid induced writhing syndrome in mice were observed with its oral administration at 1000mg/kg, and the convulsions induced by strychnine and pentetrazole were not inhibited at its oral doses of 1000mg/kg in mice. The solution of G009 as given intravenously at the doses of 30 and 60mg/kg in rabbit had no influences on blood pressure and respiration rates and depth. In isolated organs of rat uterus and fundus muscles and guinea-pig ileum and trachea, it did not show any contraction or relaxation at the concentration of 2$\times$10$^{-3}$g/ml, and the contractive actions produced by oxytocin, acetylcholine, serotonin and histamine did not inhibited by the same doses. This material showed no effect on intestinal propulsion test in mice and gastric secretion in rats at the oral doses of 1000mg/kg. However, it is interesting that the material exhibited potent inhibition of acidified aspirin induced gastric damage at the doses of 500 and 1000mg/kg in rats.