Acetylcholine에 의한 적출 십이지장 평활근 수축에 미치는 Calcium 길항제의 영향

손의동,이만기,박창호,김인겸,김중영 慶北大學校 醫科大學 1991 慶北醫大誌 Vol.32 No.2

To compare antagonistic action of caloium antagonists on intestinal smooth muscle contraction, acetylcholine-induced phasic contraction (PC) and tonic contraction (TC) initiated by different calcium utilization were observed in the presence of various calcium antagonists by the use of isolated mouse duodenum suspended in Tyrode's solution. By verapamil at 2.2×10 exp(-6), 2.2×10 exp(-5) and 2.2×10 exp(-4) mM, PC was more decreased dose-dependently than TC. By nifedipine at 7.9×10 exp(-5) mM, PC was more decreased than TC, but at 7.9×10 exp(-6) mM it did not affect PC and TC. By diltiazem at 6.1×10 exp(-4) mM, PC was more decreased than TC, but at 2.4×10 exp(-4) and 2.4×10 exp(-5) mM it did not affect both of the contractions. By cobalt chloride at 0.3, 1.3, and 2.6 mM, TC was significantly decreased without affecting PC, but PC markedly decreased at 5.2 mM. These results reconfirmed the fact that cobalt ion-induced calcium antagonism is more related to calcium influx process than calcium release process in contrast with the actions of verapamil, diltiazem, and nifedipine in duodenal smooth muscle.

소아과의원의 감기환자 처방 분석

한인희,손의동 중앙대학교 약학연구소 2002 약학 논총 Vol.16 No.-

It has been shown that the common cold is the most prevalent disease in humans generally caused by rhinovirus etc. It may be interesting if we compare pediatric's prescriptions drugs in local clinic, and find some differences to them. This research shows that antibiotic or/and antiviral drug use(s) between two pediatric's prescriptions are quite different. There are no licensed effective antiviral drugs for the common cold. Although bacterial involvement was rare and an uncomplicated common cold did not require combination treatment with antibiotics, antiviral and antibiotic therapy prescriptions increase insurance drug prices 2.59 times. When prescribed over 2 items in same efficacy drug group to patients, it will be one of the most reason of insurance fee increment. The therapeutic periods of them was not different when we compared to symptomatic and antibiotic therapy. This analysis to the pediatric's prescriptions drugs in local clinic provide the reference data for the basic guideline of standard prescriptions. Aspirin prescriptions as antipyretics-analgesics should be reinvestigated.

소아과 환자의 처방분석 및 검토

이종미,손의동 중앙대학교 약학연구소 2002 약학 논총 Vol.16 No.-

It is known that drug therapy of children is different from that of adults and the prescription is needed to the cautious, because drug's safety and dosage are not established. When the capsule is changed to powder form in pediatric patients, the effect and safety of treatment maybe lost. So I investigated the drug interactions and the alternation of dosage forms in dispensing of oral drug products for pediatric patients based on the prescriptions of Hospital A. One prescription is composed of 5.3 drugs, is prescribed an average 4.9 days and the pediatrics in hospital A used kinds of 145 drugs during January, 2002. Mucolytics are most common in prescriptions(49.6%), digestives, antibiotics, antihistamines and antipyreptics in senior. The most common disease is asthma in pediatric patients, sinusitis, rhinitis, bronchitis and pharyngitis in order. Among 11,534 prescriptions for 2,163 patients' drug interaction were found 133 cases, and most drugs belong to macrolides and asthma related drugs but not seriously. Among 21,678 prescriptions, the cases of alternation of dosage forms (tablets and capsules intended for constitution as powders) were 17,950 (83%), this result is showed that adult typed drugs are popular in pediatric department. The most common changing drug is fenoterol and the other drugs are theophylline, bromhexine, ketotifen fumarate, in order. Number of powder formed drug with decreased effectivenes, unplesant swelling and bitter tastes when powder formed are 726 cases. On the basis of the results of this study, several problems caused by the alternation were discussed, such as changes in bioavailability loss in dose, stability and the problem of feeding. It was suggested that the information in alternation must be given by the pharmaceutical manufacturer and the hospital pharmacists must consider these problems in pediatric dispensing. Above all, it was desirable to develop pediatric dosage forms by the pharmaceutical manufacturer.

천마의 항 불안 효과

김여환,최형철,손의동,이광윤,김원준,박형배,하정희 대한생물치료정신의학회 1996 생물치료정신의학 Vol.2 No.2

천마(Gastrodia elata Blume)의 근경을 말린 것은 한방에서 오래전부터 여러 형태의 간질발작 치료 목적으로 이용되어지고 있었으나 어떤 활성물질에 의해 또 어떤 작용 기전을 통해 약리작용을 나타내는지를 충분하게 설명하지 못하고 있다. 최근 항경련 작용기전 연구 결과 천마추출물의 GABA성 신경전달계에 대한 조절작용과 관련이 있을 것이라는 연구 결과가 보고되었으며, 소량으로도 뇌억제 및 진정작용이 있다는 문헌을 참고하여 볼 때 천마의 항불안 작용 가능성이 시사되었다. 이에 본 연구를 통하여 천마를 사용하여 실험동물에서 항불안 작용을 검색하고 그 작용기전의 일부를 밝히고자 항불안작용 기전에 중요한 benzodiazepine 수용체와의 상호작용을 관찰하였다. 실험 결과, 천마 추출물의 경구 장기투여는 생쥐의 elevated plus maze 검사에서 개방 통로에로의 진입 및 개방통로에서의 체류시간을 증가시킴으로써 항불안 효과를 나타내었다. 천마의 에탄올 추출물은 benzodiazepine수용체 길항제인 [³H] Ro15-1788결합을 억제하였으며, 천마 추출물은 [³H] Ro15-1788의 수용체 결합에 대한 최대 결합력(Bmax)은 변화시키지 않고, 친화력(affinity)을 감소시킴으로써 상경적인 결합 양상을 나타내었다. 또 천마의 에탄올 추출물은 benzodiazepine 수용체의 효현제인 flunitrazepam의 수용체 결합반응을 억제시켰는데, 이러한 억제는 GABA 존재하에서 항진되는 것을 관찰하였다. 이상의 결과로 미루어보아 천마의 에탄올추출물 내에는 항불안작용을 나타내는 성분이 함유되어 있을 가능성을 예상케한다. Gastrodia elata Blume is a medicinal plant which has been used as anticonvulsant in oriental medicine, and has been used as sedatives. A survey of the relevant literature has indicated that the putative anxiolytic activity of G.elata Bl. has not been scientifically investigated. Therefore, the present study was designed to assess anxiolytic property and interaction with benzodiazepine receptor of G. elata BI. The putative anxiolytic activity of ethanol extract of G. elata BI. was performed in mice using an elevated plus maze paradigm. Chronic oral administration of G. elata BI. showed anxiolytic action in mice. It was suggested that regulation of GABAergic neurotarnsmission may be important in the action of G. elata BI. The interaction of G. elata BI. with benzodiazepine receptor was investigated using rat cortices. Ethanol extract of G. elata inhibited the binding of [³H] Ro15-1788, a selective benzodiazepine receptor antagonist to benzodiazepine receptor. The inhibition of [³H] Ro15-1788 binding by G. elata BI. appeared to be competitive. Further, GABA significantly enhanced the potency of this extract in inhibiting [³H] flunitrazepam, a selective benzodiazepine receptor agonist, binding to benzodiazepine receptor. From these findings, it can be concluded that substance or substances with neurochemical properties characteristic of a benzodiazepine receptor agonist may contribute to the anxiolytic property of G. elata BI.

Streptozotocin으로 유발된 당뇨병쥐의 신경전도속도에 대한 Evening primrose oil (EPO), Vit.C, Vit.E의 약물효과

신창열,류정수,김학림,강봉수,손의동,허인회 중앙대학교 약학연구소 1997 약학 논총 Vol.11 No.-

The effects of evening primrose oil (EPO). Vit.C and Vit.E on nerve conduction velocity (NCV) in streptozotocin -induced diabetic rats were investigated. 5 weeks- diabetes caused 27±0.5 % reduction in sciatic motor conduction velocity as compared with normal control. Dietary supplement of 5% EPO. 125mg/kg Vit.C. and lg/kg Vit.E prevented significantly the development of the motor nerve conduction velocity deficit about 21±0.5, 21±0.5, 26±0.5% respectively. The total serum cholesterol and triglyceride were decreased by administration 5% EPO. Vit.C, and Vit.E as compared with diabetic control. However, the serum glucose was not decreased by administration 5% EPO. 125mg/kg Vit.C but the serum glucose was decreased by administration lg/kg Vit.E as compared with diabetic control.

Cooperation of G<FONT FACE= 바탕 >β and G<FONT FACE= 바탕 >αq Protein in Contractile Response of Cat Lower Esophageal Sphincter (LES)

Uy Dong Sohn,Tai Sang Lee 대한생리학회-대한약리학회 2003 The Korean Journal of Physiology & Pharmacology Vol.13 No.4

We previously shown that LES contraction depends on M<SUB>3</SUB> receptors linked to PTX insensitive G<SUB>q</SUB> protein and activation of PLC. This results in production of IP<SUB>3</SUB>, which mediates calcium release, and contraction through a CaM dependent pathway. In the esophagus ACh activates M<SUB>2</SUB> receptors linked to PTX sensitive G<SUB>i3</SUB> protein, resulting in activation of PLD, presumably, production of DAG. We investigated the role of PLC isozymes which can be activated by Gq or G<FONT FACE= 바탕 >β protein on ACh-induced contraction in LES and esophagus. Immunoblot analysis showed the presence of 3 types of PLC isozymes, PLC-<FONT FACE= 바탕 >β1, PLC-<FONT FACE= 바탕 >β3, and PLC-<FONT FACE= 바탕 >γ1, but not PLC-<FONT FACE= 바탕 >β2, PLC-<FONT FACE= 바탕 >β4, PLC-<FONT FACE= 바탕 >γ2, PLC-<FONT FACE= 바탕 >δ1, and PLC-<FONT FACE= 바탕 >δ2 from both LES and esophageal muscle. ACh produced contraction in a dose dependent manner in LES and esophageal muscle cells obtained by enzymatic digestion with collagenase. PLC-<FONT FACE= 바탕 >β1 or PLC-<FONT FACE= 바탕 >β3 antibody incubation reduced contraction in response to ACh in LES but not in esophageal permeabilized cells, but PLC-<FONT FACE= 바탕 >γ1 antibody incubation did not have an inhibitory effect. The inhibition by PLC-<FONT FACE= 바탕 >β1 or PLC-<FONT FACE= 바탕 >β3 antibody on Ach-induced contraction was antibody concentration dependent. The combination with PLC-<FONT FACE= 바탕 >β<SUB>1</SUB> and PLC-<FONT FACE= 바탕 >β<SUB>3</SUB> antibody completely abolished the contraction, suggesting that PLC-<FONT FACE= 바탕 >β1 and PLC-<FONT FACE= 바탕 >β3 have a synergism to inhibit the contraction in LES. PLC-<FONT FACE= 바탕 >β1, -<FONT FACE= 바탕 >β3 or -<FONT FACE= 바탕 >γ1 antibody did not reduce the contraction of LES cells in response to DAG (10<SUP>⁣6 </SUP>M), suggesting that this isozyme of PLC may not activate PKC. When G<SUB>q/11</SUB> antibody was incubated, the inhibitory effect of the incubation of PLC <FONT FACE= 바탕 >β<SUB>3</SUB>, but not of PLC <FONT FACE= 바탕 >β<SUB>1</SUB> was additive (Fig. 6). In contrast, when G<SUB><FONT FACE= 바탕 >β</SUB> antibody was incubated, the inhibitory effect of the incubation of PLC <FONT FACE= 바탕 >β<SUB>1</SUB>, but not of PLC <FONT FACE= 바탕 >β<SUB>3</SUB> was additive. This data suggest that G<SUB>q/11</SUB> or G<FONT FACE= 바탕 >β may activate cooperatively different PLC isozyme, PLC<FONT FACE= 바탕 >β<SUB>1</SUB> or PLC<FONT FACE= 바탕 >β<SUB>3</SUB> respectively.

Hepatoprotective Effects of Ginseng Intestinal Metabolite IH-901 on Chemical-Induced Hepatic Damage

Uy Dong Sohn,Sung Kwon Ko,Tae Sik Choi,Byung Ok Im,Sung Tai Han,Byung Wook Yang,Jong Hwan Sung,Yong Sung Kim,Jae Gwang Woo,Young Rae Cho,Young Sil Min,Ji Hoon Jeong,Boo Yong Lee 한국식품과학회 2005 Food Science and Biotechnology Vol.14 No.4

G Protein-Coupled Receptor Signaling in Gastrointestinal Smooth Muscle

Uy Dong Sohn,Dong Seok Kim,Karnam S Murthy 대한생리학회-대한약리학회 2001 The Korean Journal of Physiology & Pharmacology Vol.5 No.4

<P> Contraction of smooth muscle is initiated by an increase in cytosolic Ca<SUP>2⁢</SUP> leading to activation of Ca<SUP>2⁢</SUP>/ calmodulin-dependnet myosin light chain (MLC) kinase and phosphorylation of MLC. The types of contraction and signaling mechanisms mediating contraction differ depending on the region. The involvement of these different mechanisms varies depending on the source of Ca<SUP>2⁢</SUP> and the kinetic of Ca<SUP>2⁢</SUP> mobilization. Ca<SUP>2⁢</SUP> mobilizing agonists stimulate different phospholipases (PLC-β, PLD and PLA<SUB>2</SUB>) to generate one or more Ca<SUP>2⁢</SUP> mobilizing messengers (IP<SUB>3</SUB> and AA), and diacylglycerol (DAG), an activator of protein kinase C (PKC). The relative contributions of PLC-β, PLA<SUB>2</SUB> and PLD to generate second messengers vary greatly between cells and types of contraction. In smooth muscle cell derived form the circular muscle layer of the intestine, preferential hydrolysis of PIP<SUB>2</SUB> and generation of IP<SUB>3</SUB> and IP<SUB>3</SUB>-dependent Ca<SUP>2⁢</SUP> release initiate the contraction. In smooth muscle cells derived from longitudinal muscle layer of the intestine, preferential hydrolysis of PC by PLA<SUB>2</SUB>, generation of AA and AA-mediated Ca<SUP>2⁢</SUP> influx, cADP ribose formation and Ca<SUP>2⁢</SUP>-induced Ca<SUP>2⁢</SUP> release initiate the contraction. Sustained contraction, however, in both cell types is mediated by Ca<SUP>2⁢</SUP>-independent mechanism involving activation of PKC-ε by DAG derived form PLD. A functional linkage between G<SUB>13</SUB>, RhoA, ROCK, PKC-ε, CPI-17 and MLC phosphorylation in sustained contraction has been implicated. Contraction of normal esophageal circular muscle (ESO) in response to acetylcholine (ACh) is linked to M<SUB>2</SUB> muscarinic receptors activating at least three intracellular phospholipases, i.e. phosphatidylcholine-specific phospholipase C (PC-PLC), phospholipase D (PLD) and the high molecular weight (85 kDa) cytosolic phospholipase A<SUB>2</SUB> (cPLA<SUB>2</SUB>) to induce phosphatidylcholine (PC) metabolism, production of diacylglycerol (DAG) and arachidonic acid (AA), resulting in activation of a protein kinase C (PKC)-dependent pathway. In contrast, lower esophageal sphincter (LES) contraction induced by maximally effective doses of ACh is mediated by muscarinic M<SUB>3 </SUB>receptors, linked to pertussis toxin-insensitive GTP-binding proteins of the G<SUB>q/11</SUB> type. They activate phospholipase C, which hydrolyzes phosphatidylinositol bisphosphate (PIP<SUB>2</SUB>), producing inositol 1, 4, 5-trisphosphate (IP<SUB>3</SUB>) and DAG. IP<SUB>3</SUB> causes release of intracellular Ca<SUP>2⁢</SUP> and formation of a Ca<SUP>2⁢</SUP>-calmodulin complex, resulting in activation of myosin light chain kinase and contraction through a calmodulin-dependent pathway.

Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats

Dong Min Kim,Tin Myo Khing,Wynn Thein,Won Seok Choi,신창열,Uy Dong Sohn 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.6

Dysfunction of gastrointestinal (GI) motilityis a common complication in patients with diabetes mellitus(DM). Studies related to changes in fundus contractioninduced by inhibitors in DM are not well known. Therefore,this study aimed to investigate the signaling pathwaysinvolved in the changes in the contraction of fundus smoothmuscle obtained from control and DM rats. DM was inducedby injecting streptozotocin (65 mg/kg) into Sprague–Dawleyrats. The rats were sacrifi ced after 14 days. Fundus smoothmuscle contraction was stimulated using electrical fi eld stimulation(amplitude, 50 V; duration, 1 min; frequency, 2–20Hz) and acetylcholine (0.1 mM). The inhibitor-mediatedcell membrane was pre-treated with atropine, verapamil,methysergide, ketanserin, ondansetron, and GR 113808. Inhibitors related to intracellular signaling, such as U73122,chelerythrine, L -NNA, were also used. ML-9 and Y-27632were identifi ed as inhibitors of factors of myosin light chain(MLC). The contractility was observed to be lower in theDM group than in the control group. Further, the activities ofphospholipase C (PLC), protein kinase C (PKC), and myosinlight chain kinase (MLCK) were decreased in the DMgroup. DM reduced the activity of PLC, PKC, and MLCK,which resulted in a decrease in the contractility of the fundussmooth muscle. Therefore, our results present the mechanismof this DM-mediated GI disorder.

EXPERIMENTAL ESOPHAGITIS AND SIGNAL TRANSDUCTION TO SMOOTH MUSCLE MOTILITY

(Uy Dong Sohn) 한국응용약물학회 1997 학술대회 Vol.1997 No.2