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마우스 회장 운동에 대한 나문재 (Suaeda asparagoides M<sub>IQ</sub>) 추출물의 효과
송재찬,박창희,김현탁,메하리 엔델,이만휘,박승춘,김길수,김태완,Song, Jae-Chan,Park, Chang-Hee,Kim, Hyun-Tak,Endale, Mehari,Rhee, Man-Hee,Park, Seung-Chun,Kim, Kil-Soo,Kim, Tae-Wan 대한수의학회 2006 大韓獸醫學會誌 Vol.46 No.4
Suaeda (S.) asparagoides $M_{IQ}$, one of the halophyte groups, has been used as a folk remedy for digestive disturbances in Korea. However, its pharmacological activity on gastrointestinal motility has not been reported yet. In this study, the effects of this halophyte extracts with various solvent fractions (ethanol, hexane, chloroform, ethyl acetate, butanol, and water) on mice ileal spontaneous motility was examined. All solvent fractions at the concentration of $100{\mu}g/ml$ showed inhibitory actions on spontaneous motility of ileum with the potency order of water > 70% ethanol > hexane ${\gg}$ chloroform ${\geq}$ butanol ${\geq}$ ethyl acetate, respectively. In addition, the water fraction of extracts from S. asparagoides $M_{IQ}$ (WFSA) dose-dependently ($1-100{\mu}g/ml$) inhibited the amplitude of spontaneous phasic contraction and area under the contractile curve (AUC). The inhibitory effect of water fraction at the concentration of $10{\mu}g/ml$ was not affected by tetrodotoxin (TTX), $Na^+$ channel blocker ($1{\mu}M$), and $N^w$-nitro-L-arginine Methyl Ester (L-NAME), nitric oxide synthase inhibitor ($100{\mu}M$). However, cyclopiazonic acid (CPA, $10{\mu}M$), inhibitor of sarcoplasmic reticulum $Ca^{2+}$-ATPase, almost blocked the inhibitory effects of WFSA ($10{\mu}g/ml$) on the spontaneous phasic contraction of mouse ileum. But, CPA did not inhibit the lowering basal tone effects of WFSA. The result of this study showed that various extracts of S. asparagoides $M_{IQ}$ induce inhibitory effects on spontaneous contraction of mice ileal segments. More over, the polar solvent fractions were shown to be more potent than non-polar solvent fractions. The effects of S. asparagoides $M_{IQ}$ extracts are not mediated by nerve or nitric oxide. The inhibitory effects of WFSA at least partially mediated by sarcoplasmic reticulum $Ca^{2+}$-ATPase. However, further study is required to determine the exact pharmacological mechanisms of this halophyte on its gastrointestinal motility inhibitory effects.
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Sung Dae Kim(김성대),Whi Min Lee(이휘민),Mehari Endale(메하리 엔델),Jae Youl Cho(조재열),Hwa Jin Park(박화진),Jae Wook Oh(오재욱),Man Hee Rhee(이만휘) 한국생명과학회 2009 생명과학회지 Vol.19 No.11
RGS단백질은 G 단백질 신호전달작용에 있어서 신호를 억제하는 조절단백질로서 G 단백질 매개수용체(GPCR)의 활성을 억제하는 것으로 알려졌다. 그렇지만 캐너비노이드 수용체 CB2의 활성에 있어서 RGS 단백질의 조절효과에 관해서는 지금까지 알려져 있지 않다. 그러므로 본 연구에서 우리는 RGS2, 3, 4, 5와 캐너비노이드 수용체 CB2 cDNA를 동시에 HEK293 세포주에 발현시킨 후 각 RGS 단백질의 효과를 조사하였다. CB2 단백질을 발현하는 HEK293 세포주(CB2-HEK293)에서 CB2 효현제인 WIN55,212-2는 폴스콜린으로 유도된 cAMP response element (CRE) 활성을 억제하였다. 이러한 WIN55,212-2의 CRE 억제 활성은 RGS3에 의하여 차단되었지만 RGS2, 4, 및 RGS5에서는 관찰되지 않았다. 뿐만 아니라 RGS3 small interference RNA (siRNA)를 사용하여 내인성 RGS3 단백질의 발현을 저하시키면 WIN55,212-2에 의한 폴스콜린 유도 CRE 억제활성은 더욱 증강되었다. 이상의 결과는 캐너비노이드 수용체 CB2 신호전달작용에 있어서 RGS 단백질의 기능적 역할과 특히 내인성 RGS3의 캐너비노이드 수용체 CB2에 대한 선택적 작용을 나타낸다. RGS proteins have been identified as negative regulators of G protein signalling pathways and attenuate the activity of GPCR receptors. However, information on the regulatory effects of RGS proteins in the activity of cannabinoid receptors is limited. In this study, the role of RGS proteins on the signal transduction of the CB2 cannabinoid receptor was investigated in HEK293 cells co-transfected with CB2-receptors and plasmids encoding RGS2, RGS3, RGS4 and RGS5. Treatment of cells with WIN55, 212-2, a CB2 receptor agonist, inhibited forskolin-induced cAMP response element (CRE) activity in CB2-transfected HEK293 (CB2-HEK293) cells. This inhibitory effect of WIN 55, 212-2 on CRE activity was reversed by co-transfection of CB2-HEK293 cells with RGS3, but not with RGS2, RGS4 and RGS5. However, endogenous RGS3 protein knocked down by a small interfering siRNA targeting RGS3 gene enhanced inhibition of forskolin induced CRE activity via agonist induced CB2 receptor signal transduction. These results indicate the functional role of endogenous RGS protein in cannabinoid signaling pathways and define receptor-selective roles of endogenous RGS3 in modulating CRE transcriptional responses to agonist induced CB2 receptor activity.
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