• The Korean Journal of Physiology
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• 제25권2호
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• pp.147-158
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• 1991

The effects of noradrenaline on the spontaneous contraction recorded from a strip of mucosa-free antral circular muscle were studied in the guinea-pig stomach, and the changes in slow waves and membrane resistance were analyzed in order to elucidate the mechanism for the excitatory response to noradrenaline. Electrical responses of circular muscle cells were recorded using glass microelectrodes filled with 3 M KCI. Electrotonic potentials were produced to estimate membrane resistance by the partition stimulating method. 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 were potentiated dose-dependently by the application of noradrenaline. 2) Through the experiments using adrenoceptor-blockers, the strong excitatory effect via $[\alpha}-adrenoceptors$ and the weak inhibitory efffect via ${\beta}-adrenoceptors$ were noted. 3) Noradrenaline produced hyperpolarization of membrane potential, and increases in the amplitude and the maximum rate of rise of slow waves. 4) In the presence of apamin, Ca-dependent K channel blocker, the characteristic hyperpolarization was not developed. However, the excitatory effect of noradrenaline on spontaneous contraction remained. 5) Membrane resistance was reduced during the hyperpolarized state by the application of noradrenaline, and the change of membrane resistance and the hyperpolarized state were completely abolished by apamin. From the above results, following conclusions could be made: Excitatory responses to noradrenaline result from the dominant ${\alpha}-excitatory$, and the weak ${\beta}-inhibitory$ action of noradrenaline. Hyperpolarization of membrane potential by noradrenaline is due to the activation of Ca-dependent K channel.

• 대한약리학회지
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• 제19권2호
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• pp.1-8
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• 1983

Prostaglandin(PG) is ubiquitously distributed in most mammalian tissue and their actions are complicated. Especially in autonomic nervous system, there are evidences indicating that PGs act as neuromodulators i.e., PGs, which are released in the vicinity of autonomic neuroeffector junctions, influence the release and the response of the neurotransmitter. Present study was undertaken to elucidate the interrelationship between $PGF_{2\alpha}$ and adrenergic ${\alpha}_2-receptor$ function in electrical field stimulation induced contractile response of vas deferens in rat. Male rat, weighing 150{\sim}200\;g, was sacrificed and vas deferens was obtained. The isolated vas deferens strip was placed between two platinum electrodes in temperature controlled $(37^{\circ}C)$ muscle chamber containing Tyrode's solution and the electrical field stimulation(EFS) induced contraction was recorded with Grass Polygraph(Model 7) via force displacement transducer (FT .03, Grass). The results are summarized as follows: 1) Electrical field stimulation for 1sec( 1 msec, 40 cps) induced contraction of vas deferens was completely blocked by tetrodotoxin. 2) Bretylium caused marked inhibition of the EFS-induced contraction, hut tyramine and cocaine augmented the contraction. 3) EFS-induced contraction was inhibited or little affected in distal portion of vas deferens by norepinephrine or methoxamine, but the contraction was rather augmented by the ${\alpha}-agonists$ in proximal portion. 4) Clonidine inhibited the EFS-induced contraction proportionally to the concentration in distal portion, which was blocked by yohimbine pretreatment, but in the presence of $PGF_{2\alpha}$ the blockade by yohimbine was reversed. 5) Indomethacin pretreatment reduced the effect of clonidine, but addition of $PGF_{2\alpha}$ after washing-out the indomethacin caused the contraction to the control level. From these results it is suggested that PG synthesis is a necessary step and the PG itself has a permissive role in ${\alpha}_2-adrenoceptor$ action in rat vas deferens.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.11-23
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• 2003

Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.

• Journal of Acupuncture Research
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• 제20권2호
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• pp.85-97
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• 2003

Introduction : In this study, the analgesic effect and its mechanism of bee venom aqua-acupuncture on complete Freund's adjuvant-induced arthritis in rats was investigated. It has been reported from a neurochemical standpoint that bee venom exerts antinociceptive effects on inflammation and that the opioid system and adrenergic system play important roles in acupuncture analgesia. however, it is not known whether central opioid and ${\alpha}2$-adrenergic components of the intrinsic descending analgesic system are activated after bee venom aqua-acupuncture. Methods : Bee venom(1mg/kg) was subcutaneously aqua-acupunctured into Joksamni($ST_{36}$) of rats with complete Freund's adjuvant(CFA)- induced arthritis and was checked of increase in TFL. Opioid and ${\alpha}_2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist, and yohimbine as ${\alpha}_2$-adrenoceptor antagonist prior to bee venom aqua-acupuncture. Results : The following results have been obtained. 1. The tail flick latency in the rat model with adjuvant-induced arthritis was significantly decreased in 2 weeks. 2. The tail flick latency in the rat model with adjuvant-induced arthritis was increased in bee venom aqua-acupuncture group compared to the normal saline aqua-acupuncture group. 3. Analgesic effect of bee venom was antagonized by yohimbine not by naloxone pretreatment in the rat model adjuvant-induced arthritis. Conclusions : Bee venom aqua-acupuncture has an analgesic effect on the rat model of adjuvant-induced of adjuvant-induced arthritis and has antinociception mediated by ${\alpha}_2$-adrenergic system.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.1-8
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• 1993

It has been known that calcium antagonists also inhibit the radioligand binding to muscarinic and $\alpha$-adrenergic receptors and, in case of verapamil, these inhibitions may play a role in the effects of verapamil on the heart. In this study, the effects of nicardipine, nifedipine, nimodipine, diltiazem and verapamil on the binding of [$^3H$]dihydroalprenolol (DHA) to dog cardiac ${\beta}$-adrenergic receptors were examined. A single uniform [$^3H$]DHA binding site ($K_D/= 5nM\;and\;B_{max}=2600$ fmol/mg protein) was identified in dog cardiac sarcolemma. [$^3H$]DHA binding was not affected by the usual therapeutic concentrations of these calcium antagonists (nanomolar range) but in the "nonspecific"concentration ranges ($28-180{\mu}m$) these drugs inhibited [$^3H$]DHA binding to $\beta$-adrenergic receptors. Nicardipine, nifedipine, nimodipine and diltiazem competed for [$^3H$]DHA binding to ${\beta}$-adrenergic receptors with dissociation constants ($K_i$) of $28{\mu}m,\' 74{\mu}m, 39{\mu}m \;and \;35{\mu}m,$ respectively. Verapamil ($K_i=176.5 {\mu}m$) was less potent inhibitor than other drugs and this inhibition was noncompetitive; the maximal binding capacity ($B_{max}$) $300 {\mu}m$ verapamil without change in the apparent dissociation constant (4K_D$) for DHA. These results indicate that the inhibitory action of calcium antagonists at high concentrations on ${\beta}$-adrenergic receptors is not involved in the therapeutic effects of these drugs by the calcium channel blocking action.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.423-431
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• 2001

Some recent investigations revealed that vasodilatory action of adenosine is mainly not mediated by surface A2 receptor and suggested the existence of an intracellular action site. In the present study, we tried to differentiate intracellular from extracellular site of adenosine action in the regulation of coronary flow. In perfused rabbit hearts, concentration-response curve of coronary flow to exogenous adenosine was constructed in the presence or absence of dipyridamole, an inhibitor of transmembrane purine transport. Inhibition of cellular adenosine uptake by dipyridamole suppressed the increase of flow rate while enhancing the decrease in heart rate induced by exogenous adenosine. In another series of experiments, perfused rabbit hearts were subjected to energy deprivation in order to increase the production of endogenous adenosine. Energy deprivation along with dipyridamole administration resulted in higher coronary flow rate. Lower perfusate adenosine concentration was observed along with higher tissue adenosine content in this group. These results implied that coronary flow rate is determined not by interstitial adenosine concentration but by intracellular activity of adenosine. To confirm the effects of dypiridamole in vivo, direct measurement of interstitial adenosine concentration by mycrodialysis along with the assay of intracellular adenosine content was performed after intranenous dipyridamole administration. After dipyridamole infusion, intracellular adenosine content was markedly increased while interstitial adenosine concentration was not altered. In another series of experiments, the right shift of concentration-response curve of adenosine-induced vasodilation by 8-phenyltheophilline, a representative adenosine receptor antagonist, was mostly abolished by prior administration of prazosin, indicating that the influence of 8-PT on the adenosine action is not attributed to the inhibition of A2 receptor but related to the suppression of ${\alpha}-adrenoceptor$ activation. From these results, we concluded that adenosine acts intracellularly to regulate the coronary blood flow.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.285-289
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• 2010

In the present study, the antinociceptive profiles of $Campanula$ $punctata$ extract were examined in ICR mice. The $Campanula$ $punctata$ contain a large dose of saponin. $Campanula$ $punctata$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Campanula$ $punctata$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7{\mu}g$) was diminished by $Campanula$ $punctata$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Campanula$ $punctata$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Campanula$ $punctata$ extract in the writhing test. Our results suggest that $Campanula$ $punctata$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Campanula$ $punctata$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• 대한수의학회지
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• 제37권3호
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• pp.533-540
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• 1997

To elucidate the effects of purinergic nerve on relaxation of pig coronary artery, the effects of ATP, 2-methylthio ATP and electrical perivascular nerve stimulation were investigated from physiograph on the isolated coronary artery of pig. The results btained were as follows; 1. The relaxative responses induced by perivascular nerve stimulation(20V, 0.5msec, 10sec) were the frequency(1~8Hz) dependent manner with phentolamine($10^{-5}M$) and atropine($10^{-6}M$) on isolated coronary artery of pig. 2. The relaxative responses induced. by adenosine($10^{-7}{\sim}5{\times}10^{-3}M$) or ATP($10^{-7}{\sim}5{\times}10^{-5}M$) on precontraction with histamine($10^{-5}M$) were the dose-dependent manner, but the contractile responses were often induced by ATP($10^{-4}M$ and $10^{-3}M$). 3. The relaxative responses induced by 2-methylthio ATP($2.5{\times}10^{-8}{\sim}2.5{\times}10^{-6}M$) on precontraction with histamine($10^{-5}M$) were the dose-dependent manner. 4. The relaxative response induced by 2-methylthio ATP($10^{-7}M$) on precontraction with histamine($10^{-5}M$) was completely blocked by the pretreatment with $P_{2Y}$-purinoceptor blocker, reactive blue 2($10^{-4}M$). 5. The neurogenic relaxative response induced by perivascular nerve stimulation(20V, 8Hz, 0.5msec, 10sec) was weakly inhibited by the pretreatment with ${\beta}$-adrenoceptor blocker, propranolol($10^{-5}M$) and blocked by the addition with $P_{2Y}$-purinoceptor blocker, reactive blue 2($10^{-4}M$). The results suggest that the purinergic nerve is innervated, and its relaxative response was mediated by $P_{2Y}$-purinoceptor on isolated coronary artery in pig.

• Korean Journal of Acupuncture
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• 제23권2호
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• pp.113-123
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• 2006

Objectives: Pharmacopuncture which is a combination of acupuncture and herbal medicine helps to prevent and treat the diseases and symptoms including various pains. However, little was known about the therapeutic effects and its mechanisms on acute pain, although pharmacopuncture has been used frequently in acupuncture clinics. Acupuncture is known for producing analgesia for persistent ankle sprain pain in human. Furthermore, it also produces analgesia in a rat model of ankle sprain pain. Methods: To illuminate the underlying mechanisms of capsaicin pharmacopuncture-induced analgesia, weight bearing force (WBF) was observed on the acute ankle sprained rat model. Ankle sprain was induced in the rat by manually hyper-extending ligaments of the right ankle. Capsaicin pharmacopuncture was applied to SI6 (Yanglo) on the left forelimb (contralateral to the sprained ankle). Results: In behavioral test, capsaicin pharmacopuncture produced marked analgesic effects on acute ankle sprained animals as measured by WBF of the affected limb similar to manual acupuncture. Capsaicin pharmacopuncture was also suppressed by serotonin (5-HT) receptor antagonist methysergide (2 mg/kg, Lp.), but not by opioids receptor antagonist naltrexone (10 mg/kg, Lp.) and alpha adrenoceptor antagonist phentolamine (5 mg/kg, Lp.). Conclusion: The data suggest that capsaicin pharmacopuncture-induced analgesia is accomplished by activating the descending serotonergic inhibitory systems.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.387-392
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• 2008

Alfuzosin, an Alphal-adrenoceptor antagonist is used for the treatment of patients with voiding and in a lesser extent storage lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). The objective of this study was to formulate sustained release alfuzosin HCl granules and assess their formulation variables. The $Eudragit^{(R)}$ as a polymer, sustained release membrane, and dibutyl sebacate (DBS) as a plasticizer were used. Multi-coated alfuzosin HCl delivery systems composed of sugar sphere, various excipients, $Eudragit^{(R)}$ and HPMC (hydroxy propyl methyl cellulose), Cellulose Acetate were prepared by fluid-bed coater. Membrane layer were used $Eudragit^{(R)}$ RS PO and NE 30D. And the alfuzosin HCl coated beads were coated immediate release drug layer for initial burst. Its dissolution test was carried out compared to conventional products ($XATRAL^{(R)}$ XL). The release rate of drug from coated beads was higher than that from $XATRAL^{(R)}$ XL in pH 6.8.