• 생명과학회지
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• 제19권5호
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• pp.664-670
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• 2009

지방분해와 열생산에 관여한다고 알려진 ADRB3 유전자의 염기서열 분석을 통하여 한국인에서 호발하는 유전자 다형성 부위를 먼저 확인한 후 이 유전자 다형성들과 HDL-C와의 연관성에 대하여 조사하고자 2006년 5월에서 12월 사이에 부산지역의 일개 대학병원에서 건강진단을 받은 991명을 대상으로 신장, 체중, 체질량지수, 허리둘레, 고밀도 지단백 콜레스테롤, 중성지방, 공복 혈당을 측정하였으며, 대상자들의 혈액에서 DNA를 분리하여 ADRB3 유전자에서 흔히 발생하는 유전자다형성 부위를 확인하였다. 연구결과 한국인에서 ADRB3 유전자의 intron2 +3893T>C의 변이를 처음으로 발견하였으며 열성 대립형질의 발현빈도는 0.164이었다. Exon1의 +188T>C와 intron2의 +3893T>C의 열성 대립형질인 C형이 있을 경우 HDL-C의 농도가 낮았다. 따라서 ADRB 유전자 다형성은 HDL-C과 관련이 있을 것으로 생각된다.

• The Korean Journal of Physiology
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• 제11권2호
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• pp.33-39
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• 1977

It has been reported that administration of Ginseng powder to the Guinea pig reduces anaphylactic shook induced by horse serum (Lee, 1939). However, Lee et al. (1960) and Paik et al. (1976) have demonstrated that Ginseng increases capillary permeabilites and histamine release from the mast cell. These facts suggest that Ginseng acts directly on the bronchial muscle causing it to dilate. Recently, a number of investigators(Kidakawa & Iwasiro 1963; Takagi et al. 1973) have reported that Ginseng reverses acetylcholine- or histamine- induced contraction in the isolated Guinea pig ileum. We, therefore, undertook the present study to examine if Ginseng relaxes the spasm of bronchial muscle induced by acetylcholine or histamine. We have also attempted to identify the mechanism of the Ginseng effect. Male Guinea Pig was sacrificed by a blow on the head, The trachea was removed and sectioned with scissors into about 12 rings. After the 'C' shaped ring of cartilage was sectioned the one end of ring was tied to the bottom of the incubation bath and the other end was connected to a force transducer (FTO 3C) to record tension on a Polygraph. When the antispasmodic action of Ginseng effect was first examined in the normal trachea which was not treated by the drug. And then the Ginseng effect was tested in the muscle treated by histamine hydrochloride, acetylcholine hydrochloride or barium chloride. The results indicate that Ginseng alcohol extract relaxes the contraction of isolated tracheal muscle induced by histamine $(1{\mu}g/ml{\sim}10{\mu}g/ml)$, acetylcholine $(1{\mu}g/ml{\sim}5{\mu}g/ml)$ and barium chloride (1.5 mg/ml). The mechanism of this action is in Pa.1 due to nonspecific antimuscarinic and antihistaminic effect and in part by predominant action in the adrenergic ${\beta}-receptor$ although the ${\alpha}-receptor$ is also involved. We, therefore, conclude that Ginseng can be act as a bronchodilator.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.207-213
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• 2007

This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide and neurotransmitters such as serotonin($5{\mu}M$), histamine($20{\mu}M$), and carbarchol(CCh, $10{\sim}50{\mu}M$) did not produce significant contraction. However, CCh($50{\mu}M$) produced slow phasic contraction in the presence of 25 mM $K^+$. Cyclopiazonic acid(CPA, $10{\mu}M$), SR $Ca^{2+}$-ATPase blocker, produced tonic contraction(0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone(CCCP) also produced weak tonic contraction(0.01 mN). The possible involvement of $K^+$ channels was also pursued. Tetraethyl ammonium chloride(TEA, 10 mM), glibenclamide($10{\mu}M$) and quinidine($20{\mu}M$) which are known to block $Ca^{2+}$-activated $K^+$ channels($K_{Ca}$ channel), ATP-sensitive $K^+$ channels($K_{ATP}$) and nonselective $K^+$ channel, respectively, did not elicit any significant effect. However, $Ba^{2+}$($1{\sim}2mM$), blocker of inward rectifier $K^+$ channels($K_{IR}$ channel), produced phasic contraction in a reversible manner, which was blocked by $1{\mu}M$ nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type $Ca^{2+}$ channels($VDCC_L$) in smooth muscle membrane. This $Ba^{2+}$-induced phasic contraction was significantly enhanced by $10{\mu}M$ cyclopiazonic acid(CPA) in the frequency and amplitude. Finally, regulation of $Ba^{2+}$-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and $\beta$-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of $Ba^{2+}$-induced contraction(p<0.05). These results suggest that $Ba^{2+}$ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and $\beta$-adrenergic stimulation.

• Journal of Nutrition and Health
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• 제28권2호
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• pp.115-126
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• 1995

The effects of energy-yielding substrates on coronary circulation, myocardial oxygen metabolism, and intramyocytic adenylates of perfused Wistar control rat(WC) and spontaneously hypertensive rat(SHR) hearts were examined under basal and $\beta$-adrenergic stimulation conditions. The perfusion medium (1.0mM Ca2+) contained 5mM glucose (+5U/l insulin) in combination with 5mM pyruvate, 5mM lacate, 5mM acetate, or 5mM octanoate as energy substrates. Hearts were perfused with each substrate buffer for 20min under basal conditions. Coronary functinal hyperemia was induced by infusing for 20min isoproterenol (ISO, 1uM), a $\beta$-receptor agonist. Cardiac adenylates, glycolytic intermediates, and coronary venous lactate were measured by using an enzymatic analysis technique. Under basal conditions, acetate and octanoate significantly increased coronary flow(CF) of WC in parallel with myocardial oxygen consumption. However, CF of SHR was partly attenuated by coronary vasoconstriction despite metabolic acidosis. In addition, pyruvate and lactate depressd ISO-induced coronary functional hyperemia in SHR. It should be noted that octanoate exhibited coronary dysfunction under ISO conditions. On the other hand, fat substrates depleted myocardial high energy phosphate pool and accumulated breakdown intermediates. In SHR with coronary vasoconstriction under basal conditions, and with depressed coronary functional hyperemia, high energy phosphates were greatly depleted. These results suggest that energy substrates in the myocardium and coronary smooth muscle alter remarkably coronary circulation, and that coronary circulatory function is associated with a reserve of high energy phosphates and a balance between breakdown and nono synthesis of energy phosphates. These findings could be explained by alterations in the cytosolic redox state manipulated by LDH and hence in the cytosolic phosphorylation potential, which might be involved in hypertension of SHR.

• Journal of Ginseng Research
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• 제36권2호
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• pp.176-189
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• 2012

This study examined the effects of Korean red ginseng (KRG) on obese women and aimed to confirm that the effects of KRG on obesity differ dependently on a gene. Fifty obese women were recruited and randomized to receive KRG (n=24) or placebo (n=26) for 8 wk. Measurements of blood pressure, height, weight, waist circumference, waist-hip ratio (WHR), total fat mass, percentage of body fat, resting metabolic rate, basal body temperature, and daily food intake (FI), blood test (serum lipid, liver and renal function), Korean version of obesity-related quality of life scale (KOQOL), and a gene examination were performed. Comparisons of subjects before and after the administration of KRG revealed significant improvements of obesity in terms of weight, body mass index (BMI), WHR, FI, and KOQOL. However, in the comparison between KRG group and placebo group, only KOQOL was significantly different. KRG displayed significant efficacy on BMI and KOQOL in the CT genotype of the G protein beta 3 gene, but not in the CC genotype, on blood sugar test in the Trp64/Arg genotype of the beta 3 adrenergic receptor gene, but not in Trp64/Trp genotype, on KOQOL in the DD genotype of the angiotensin I converting enzyme gene, but not in the ID and DD genotypes. The effects of KRG on obesity were confirmed to some extent. However, a distinct effect compared to placebo was not confirmed. KRG is more effective for improving the secondary issues of the quality of life derived from obesity rather than having direct effects on the obesity-related anthropometric assessment and blood test indices.

• 대한약리학회지
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• 제2권1호
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• pp.21-29
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• 1966

Dichloroisoproterenol(DCI) i; one of the well known ${\beta}$-adrenergic receptor blocking agents. According to Moran and Perkins, DCI has sympathomimetic like action in relatively low concentrations. Fleming and Hawkins confirmed that DCI acts upon the receptors concerned with positive chronotropic and inotropic actions in the heart. Vogins reported that DCI, in concentration of $5{\times}10^{-8}$ to $5{\times}10^{-6}g/ml$, had properties of sympathomimetic amine causing positive inotropic and chronotropic actions in normal rat atria. And James and Nadeau found that DCI had not only adrenergic blocking effect in moderate and higher concentrations, but it also blocked the effect on the sinus node by vagal stimulation and of directly administered acetylcholine in higher concentrations. As stated above by many authors, DCI has complicated actions according to its concentrations. Our aim at the present experiments was to study the effects of DCI to the action of ouabain and acetylcholine upon the excised rabbit atria, as well as to the action of barium chloride and acetylcholine upon the excised rabbit intestine. In addition, Pan ax Ginseng is widely used as tonics in oriental nations, its pharmacological action, however, has not been clearly established. So we atempted to investigate the effects of the water extract of Panax Ginseng to the action of ouabain and DCI upon both atria and intestine. The results obtained were as follows. 1) DCI has a negative inotropic effect on the excised rabbit atria at concentration of $10^{-5}$ and a positive inotropic effect at concentration of $10^{-6}$. 2) DCI (at concentration of $10^{-6}$) potentiates the positive inotropic effect of ouabain upon the excised rabbit atria. 3) DCI antagonizes the action of acetylcholine upon the excised rabbit atria. 4) The water extract of Panax Ginseng, at concentration of $10^{-3}$, decreases the contractile force of rabbit atria, and tends to slightly increase that of rabbit atria at $10^{-4}$. 5) The water extract of Panax Ginseng exhibits a synergistic action with ouabain on the contractile force of rabbit atria. 6) DCI, in concentrations of $10^{-7}{\sim}10^{-6}$, depresses the tone and amplitude of contraction of the excised rabbit intestine. The depression of the intestinal tone markedly appears in pretreatment with reserpine 2mg/kg 24 hours. 7) DCI antagonizes the contractile effect of barium chloride on the excised rabbit atria. 8) DCI has no significant influence on the action of acetylcholine upon the excised rabbit intestine. 9) The series of those evidences indicates that DCI has a sympathomimetic-like action and more over a relaxing action directly on the excised rabbit intestine. 10) The water extract of Panax Ginseng in concentrations of $10^{-4}{\sim}10^{-3}$, has transient depression of the intestinal tone, but later gradually recovers its normal motility: 11) The water extract of Panax Ginseng has a synergistic action with ouabain on the intestinal contractility.

• 대한약리학회지
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• 제16권1호
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• pp.41-50
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• 1980

Chenodeoxycholic acid(CDCA) has been used as a gallstone dissolving agent since 1972. Recently, ursodeoxycholic acid(UDCA) has been reported to be effective in dissolving gallstones. Both bile acids increased bile flow. The increase in bile flow associated with an increase in cholesterol level in bile after CDCA or UDCA infusion was reported. In this study, using the smooth muscle strips of guinea pig and fowl, responses of the cholates were observed. In addition, the influence of adrenergic blocking agents on the response of the strips to cholates was investigated. Also the effects of cholates on cardiac function were examined by using isolated atria of rabbit and heart of anesthetized frog. The results are as follows: 1) All cholates, such as UDCA, CDCA, and CA produced a marked inhibitory effect on the motility in isolated duodenal strip of guinea pig and fowl, however, only UDCA showed the contraction in the isolated esophagus of fowl. These effects of cholates were blocked by propranolol. 2) In isolated guinea pig stomach strip and gall bladder, cholates exhibited a marked inhibitory effect on the motility and the effects due to UDCA and CA were blocked by phenoxybenzamine while CDCA was not affected. 3) The spontaneous and ouabain induced arrhythmia was partially abolished by cholates. However, concomitant administration of cholates with ouabain or epinephrine caused a marked prolongation in occurrence of atrial arrhythmia in comparison with ouabain or epinephrine alone in isolated rabbit atria. 4) In the heart of anesthetized frog, the epinephrine-induced arrhythmia was partially abolished by cholates. The combined treatment with cholates and ouabain or epinephrine produced a marked prolongation in occurrence of the arrhythmia in comparison with, ouabain or epinephrine alone. From the above results, it can be suggested that the effects of cholates on the smooth muscle of duodenum and esophagus are produced in response to adrenergic ${\beta}$-receptor and the effect or gall bladder and stomach is more likely due to the direct effect on the muscle. In addition, cholates exhibit a slight antiarrhythmic effect on heart, therefore, cholates can be classified as a nonselective antiarrhythmic drug, such as propranolol.

• The Korean Journal of Pain
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• 제13권2호
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• pp.156-163
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• 2000

Background: Peripheral nerve injury sometimes leads to chronic neuropathic pain such as causalgia. A subset of patients with causalgia have a sympathetically maintained pain which is often evoked by cooling stimuli. However, our knowledge on adrenergic receptor types responsible for cold-evoked pain that is sympathetically dependent is lacking. The present study was conducted to investigate subtypes of adrenoceptors involved in mediating cold-evoked pain that developed following peripheral nerve injury. Methods: Neuropathic surgery was performed by a unilateral ligation of L5 and L6 spinal nerves of rats. Behavioral sign of cold-evoked pain was examined for 5 min by measuring cumulative duration of time that the rat lifted its foot off a metal plate held at cold temperature ($5^{\circ}C$). Whether cold-evoked pain behavior was affected by antagonists of various subtypes of adrenoceptors, which were administered intraperitoneally before and after the ligation, was investigated. Results: After ligation, duration of foot lifting on the ligated side at cold temperature increased as compared to the pre-operative period. This increase maintained for the entire 40-day test period. Pretreatment with alpha-antagonist phentolamine produced a suppression of cold-evoked pain behavior that was not affected by beta-antagonist propranolol pretreatment. Prazosin, alpha-1 antagonist, suppressed cold- evoked pain behavior when treated either before or after nerve ligation. On the other hand, alpha-2 antagonist yohimbine was without effect on cold-evoked pain behavior whether it was treated before or after the ligation. Conclusions: The results suggest that peripheral nerve injury develops cold-evoked pain that is sympathetically dependent, and that alpha-1 adrenoreceptor plays a critical role for the generation of this type of pain in its initiation as well as maintenance.

• Nutrition Research and Practice
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• 제9권6호
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• pp.606-612
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• 2015

BACKGROUND/OBJECTIVES: Several medicinal properties of Smilax china L. have been studied including antioxidant, anti-inflammatory, and anti-cancer effects. However, the antiobesity activity and mechanism by which the water-soluble fraction of this plant mediates its effects are not clear. In the present study, we investigated the lipolytic actions of the water-soluble fraction of Smilax china L. leaf ethanol extract (wsSCLE) in 3T3-L1 adipocytes. MATERIALS/METHODS: The wsSCLE was identified by measuring the total polyphenol and flavonoid content. The wsSCLE was evaluated for its effects on cell viability, lipid accumulation, glycerol, and cyclic adenosine monophosphate (cAMP) contents. In addition, western blot analysis was used to evaluate the effects on protein kinase A (PKA), PKA substrates (PKAs), and hormone-sensitive lipase (HSL). For the lipid accumulation assay, 3T3-L1 adipocytes were treated with different doses of wsSCLE for 9 days starting 2 days post-confluence. In other cell experiments, mature 3T3-L1 adipocytes were treated for 24 h with wsSCLE. RESULTS: Results showed that treatment with wsSCLE at 0.05, 0.1, and 0.25 mg/mL had no effect on cell morphology and viability. Without evidence of toxicity, wsSCLE treatment decreased lipid accumulation compared with the untreated adipocyte controls as shown by the lower absorbance of Oil Red O stain. The wsSCLE significantly induced glycerol release and cAMP production in mature 3T3-L1 cells. Furthermore, protein levels of phosphorylated PKA, PKAs, and HSL significantly increased following wsSCLE treatment. CONCLUSION: These results demonstrate that the potential antiobesity activity of wsSCLE is at least in part due to the stimulation of cAMP-PKA-HSL signaling. In addition, the wsSCLE-stimulated lipolysis induced by the signaling is mediated via activation of the ${\beta}$-adrenergic receptor.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.383-389
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• 2017

Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.