• 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 Journal of Korean Medicine
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• v.30 no.6
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• pp.9-16
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• 2009

Objectives: To clarify the effects of Jungri-tang Gamibang on accelerating small intestinal movement induced by the stimulation of cholinergic neurotransmission. Methods: 500, 250 and 125mg Jungri-Tang Gamibang or 20mg domperidone were dissolved or suspended in distilled water and orally pretreated on the carbachol-accelerated small intestinal transit mice once a day for 7 days at a volume of 10ml/kg (of body weight) using a Zonde needle attached to 1 ml syringes containing test drugs. Result: Significantly (p<0.01) increase of % regions of activated charcoal transit in the small intestine was detected in carbachol control compared to that of intact control. However, significant (p<0.01) decreases of % regions of activated charcoal transit were dose-dependently observed in all Jungri-Tang Gamibang extracts or domperidone-pretreated groups. Conclusions: it was concluded that Jungri-tang Gamibang enhancement in the normal intestinal motility and normalization in the accelerated intestinal motility might interfere with a variety of muscarinic, adrenergic and histaminic receptor activities or with the mobilization of calcium ions required for smooth muscle contraction non-specifically.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.143-151
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• 2010

In Vivo and In vitro antispasmodic effects of Jun-Si-Baek-Chul-San, a Traditional Korean Polyherbal Medicineconsisted of 7 types of herbs were observed in the present study. To clarify the effects of Jun-Si-Baek-Chul-San, on accelerating small intestinal movement induced by the stimulation of cholinergic neurotransmission, we evaluated the effects of Jun-Si-Baek-Chul-San on In vivo carbachol (an acetylcholinergic agent)-accelerated mice small intestinal transit and on In vitro contractions induced by low-frequency electrostimulation, KCl, histamine or acetylcholine using isolated guinea pig ileum. To induce the acceleration of mice small intestinal transit, Carbachol 1 mg/kg was once subcutaneously dosed 15min before last administration of the test drugs. In the present study, Jun-Si-Baek-Chul-San 500, 250 and 125 mg/kg or domperidone 20 mg/kg were orally pretreated on the carbachol-accelerated mice small intestinal transit once a day for 7 days and the small intestinal transit rateof activated charcoal powder were monitored. In vitro assays, Jun-Si-Baek-Chul-San1, 0.1, 0.01 and 0.001 mg/ml or domperidone $2{\times}10^{-5}M$ were treated 10min before ileal contraction was induced by filed stimulation, acetylcholine, KCl and histamine, and the % changes of contractions were observed compared to the treatment of inducer alone. In spontaneous contraction, the % changes of contractions were observed compared to treatment of vehicle alone at 10min after Jun-Si-Baek-Chul-San or domperidone treatment. The efficacy of Jun-Si-Baek-Chul-San was compared to those of domperidone. High concentration, 1 mg/ml of Jun-Si-Baek-Chul-San was found to decrease the spontaneous contraction of the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San decrease contractions induced by electrostimulation, acetylcholine, histamine and KCl in the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San effectively inhibited the accelerated small intestinal movement induced by carbachol stimulation of cholinergic neurotransmission in In vivo. Based on the results, although the exact molecular or action mechanism and which herbs or compound in Jun-Si-Baek-Chul-San are responsible for actions, it was concluded that Jun-Si-Baek-Chul-San normalization in the accelerated intestinal motility might be interfere with a variety of muscarinic, adrenergic and histaminic receptor activities or with the mobilization of calcium ions required for smooth muscle contraction non-specificly. Therefore, it is expected that Jun-Si-Baek-Chul-San will be promising as a prescription of clinical treatment of digestive tract disorders such as accelerated the motility of intestine, diarrhea or intestinal painful contractions.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.119-128
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• 1997

The relaxation of gastric fundus smooth muscles is the primary physiological event which induces the receptive relaxation of monogastric animals. L-arginine/Nitric oxide(L-arg/NO) system is known to mediate the inhibitory non-adrenergic non-cholinergic(NANC) neurotransmission in various tissues including gastrointestinal smooth muscles. The longitudinal smooth muscles of porcine gastric fundus showed fast relaxation during electrical field stimulation(EFS) and rebound contraction after EFS in NANC condition. So, the purpose of present study was elucidation of the neurotrasmitters related to the NANC relaxation and explanation of the relation between NANC relaxation and L-arg/NO system. The longitdinal smooth muscles of porcine gastric fundus were hung in the organ bath and under the presence of guanethidine($5{\times}10^{-5}M$), precontraction was induced by carbachol($1{\times}10^{-6}M$). The muscle responses to EFS and drugs were isomerically recorded. The rusults were summarized as follows. 1. The longtudinal muscles of porcine gastric fundus showed frequency-dependent relaxation and rebound contraction to electrical field stimulaton(1ms, 8V, 1~16Hz, 20sec, EFS). These responses were blocked by tetrodotoxin($1{\times}10^{-6}M$). 2. The relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus to EFS were inhibited by L-NAME($2{\times}10^{-5}M$). The inhibitory effect of L-NAME was antagonized by L-arginine($1{\times}10^{-3}M$), but not by D-arginine($1{\times}10^{-3}M$). 3. Exogenous NO($NaNO_2$, $1{\times}10^{-5}{\sim}1{\times}10^{-4}M$, pH=2.0) caused concentration-dependent relaxation as EFS did. 4. Methylene Blue($2{\times}10^{-5}M$), a soluble guanylate cyclase inhibitor, inhibited the relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus induced by EFS, but N-ethlmaleimide, a adenylate cyclase inhibitor, did not. 5. 8-Br-cGMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cGMP analogue, induced dose-dependent relaxation. but 8-Br-cAMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cAMP analogue, did not. Both did not evoked rebound contraction. 6. ${\alpha}$-chymotrypsin did not affect the relaxation of the longitudinal muscles of porcine gastric fundus. 7. Reactive blue 2($1{\times}10^{-4}M$, 40min) siginificantly inhibited the rebound contraction induced by EFS and inhibited contraction caused by exogenous ATP($1{\times}10^{-4}{\sim}1{\times}10^{-3}M$). These results suggests that NANC relaxation of the longitudinal muscles of porcine gastric fundus mainly mediated by NO and the rebound contraction is related to NO and other neurotransmitters.