가토(家兎) 신장기능(腎臟機能)에 미치는 측뇌실내(側腦室內) Ouabain의 영향(影響)

이신웅,Lee, Shin-Woong 대한약리학회 1976 대한약리학잡지 Vol.12 No.1

It has been reported that many of the effects of digitalis glycosides could be mediated partly through the central nervous system. In this study the effects of ouabain given directly into the lateral ventricle of the brain on the renal function of the rabbit were investigated. Intraventricular ouabain elicited antidiuresis in doses ranging from 0.1 to $3\;{\mu}g$, exhibiting a rough dose-response relationship, and decreased the renal plasma flow, glomerular filtration rate and urinary excretion of sodium and potassium, concomitant with the decrease of urine flow. These decreases in urine flow, excretory rate of electrolytes significantly correlated with the decrease in renal plasma flow or glomerular filtration rate, suggesting that the antidiuresis might have been induced by the hemodynamic changes. Intravenous ouabain in a dose of $1\;{\mu}g$ did not affect the renal function. Systemic blood pressure as well as cardiac activity was not affected by the intraventricular ouabain. Effects of the intraventricular ouabain on renal function were abolished by the intravenous phentolamine-pretreatment but not affected by intraventricular phentolamine-pretreatment. Neither vasopressin infusion nor hydration did affect the renal effects of intraventricular ouabain. From these observations, it is suggested that the antidiuresis of intraventricular ouabain is induced by the increased sympathetic influence to the kidney.

Binding Profiles of Oxomemazine to the Muscarinic Receptor Subtypes

이신웅,김정구,Lee, Shin-Woong,Kim, Jeung-Gu The Korean Society of Pharmacology 1994 대한약리학잡지 Vol.30 No.1

Oxomemazine이 muscarinic receptor subtypes에 대하여 선택성을 가지는지에 관한 지견을 얻고자, 대뇌, 심실 및 회장 muscarinic receptor에 대한 oxomemazine의 결합성질을 조사, 비교하였다. $[^3H]QNB$ 포화결합실험 결과 세 조직의 muscarinic receptor는 $[^3H]QNB$에 대해서는 affinity가 약 60pM인 단일 receptor인 것으로 추정되었다. 대뇌에서 pirenzepine과 oxomemazine의 $[^3H]QNB$ 결합억제에 대한 Hill coefficient는 각각 0.67 및 0.8로서 대뇌에는 이들 약물에 대하여 affinity가 서로 다른 두 종류의 muscarinic receptor subtypes가 존재하는 것으로 나타났으며, pirenzepine에 대한 high $affinity(M_1)$와 $low affinity(M_2)$ receptor 및 oxomemazine에 대한 high $affinity(O_H)$와 $low\;affinity (O_L)$ receptor의 분포비는 약 60:40 및 40:60이었고, $M_1$과 $M_2$ receptor에 대한 pirenzepine의 $K_i$치는 16nM 및 431 nM, $O_H$와 $O_L$, receptor에 대한 oxomemazine 의 $K_i$치는 80nM 및 1350nM이었다. 그러나 심실과 회장에서 이들 약물의 $[^3H]QNB$ 결합억제에 대한 Hill coefficient는 1에 가까웠다. 심실과 회장 muscarinic receptor에 대한 pirenzepine의 $K_i$치는 850nM 및 250nM, oxomemazine의 $K_i$치는 1460nM 및 670nM로서 대피에서 이들 약물의 low affinity receptor에 대한 $K_i$치에 가까웠다. 즉, muscarinic receptor에 대한 affinity면에서 oxomemazine은 pirenzepine과 같이 대뇌에서 가장 높았으며, 회장에 대해서는 중등도였고, 심실에서 가장 낮았다. 이로 보아 oxomemazine은 $M_1\;receptor$에 선택성이 있는 것으로 추정된다. The binding properties of oxomemazine to muscarinic receptors using the ability of oxomemazine to inhibit $[^3H]QNB$ binding in membrane fractions of rat cerebrum and guinea pig ventricle and ileum were investigated. $[^3H]QNB$ bound to a single class of muscarinic receptors with a dissociation constant of approximately 60 pM in three tissue preparations. Pirenzepine and oxomemazine inhibited $[^3H]QNB$ binding in cerebrum with a Hill coefficient lower than unity, and the inhibition data were best described by a two-site model. The relative densities of the high $(M_1)\;and\;low\;(M_2)$ affinity sites for pirenzepine were 60 and 40%, with corresponding Ki values of 16 and 431 nM, and those $(O_H\;and\;O_L)$ for oxomemazine 40 and 60%, with corresponding Ki values of 80 and 1350 nM. However, the inhibition data of both drugs vs $[^3H]QNB$ in ventricle and ileum appeared to obey the law of mass-action (Hill coefficient close to 1). The apparent Ki values of pirenzepine were 850 and 250 nM, and those of oxomemazine 1460 and 570 nM in ventricle and ileum, respectively. Thus, oxomemazine like pirenzepine has high affinity for cerebrum, moderate affinity for ileum and low affinity for ventricle. These results suggest that oxomemazine could recognize the muscarinic receptor subtypes with a high affinity for the $M_1$ sites.

수종 식물추출물의 항히스타민작용

이신웅(Shin Woong Lee),이윤주(Yeun Ju Lee),손종근(Jong Keun Son) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.1

The antihistaminic action of eighteen herbal medicines was investigated by the radioligand binding and functional assays. The hexane fractions of Trichosanthis radix, Mori cortex radicis and Evodiae fructus dose-dependently inhibited [³H]mepyramine binding to H₁ receptor in guinea-pig brain homogenates and histamine-induced contraction of isolated guinea-pig ileum. Antihistaminic action of the hexane and ethyl acetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus was more potent than their antimuscarinic action evaluated from the inhibition of [³H]QNB binding and carbachol response. The ethyl acetate and chloroform fractions from Scutellariae radix also inhibited histamine-induced contraction, but antihistaminic potencies of these fractions were almost identical with their antimuscarinic potencies. The hexane fractions of Mori cortex radicis and Evodiae fructus inhibited selectively the increase of histamine-induced cutaneous vascular permeability in the rat dorsal skins. However, the ethyl acetate fraction from Scutellariae radix inhibited eqipotently the effects of histamine and serotonin on the vascular permeability. These results demonstrate that the hexane and ethyl acetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus have the selective histamine H₁ receptor blocking activity.

항 Histamine제와 Muscarinic Receptor와의 상호작용(II) -대뇌 Muscarinic M1 Receptor에 대한 작용-

이신웅(Shin Woong Lee),박영주(Young Joo Park),박인숙(In Sook Park),이정수(Jeung Soo Lee) 대한약학회 1990 약학회지 Vol.34 No.4

A single uniform population of specific, saturable, high affinity binding site of [3H] guinuclidinyl benzilate(QNB) was identified in the rat cerebral microsomes. The Kd value(37.2pM) for [3H]QNB calculated from the kinetically derived rate constants was in agreement with the Kd value(48.9pM) determined by analysis of saturation isotherms at various receptor concentrations. Dimenhydrinate(DMH), histamine H1-blocker, increased Kd value for [3H] QNB without affecting the binding site concentrations and this effect resulted from the ability of DMH to Slow [3H]QNB-receptor association. Pirenzepine inhibition curve of [3H]QNB binding was shallow(nH = 0.52) indicating the presence of two receptor subtypes with high (M1-site) and low(M2-site) affinity for pirenzepine. Analysis of these inhibition curves yielded that 68% of the total receptor populations were of the M1-subtype and the remaining 32% of the M2subtype. Ki values for the M1- and M2-subtypes were 2.42nM and 629.3nM, respectively. Ki values for H1-blockers that inhibited [3H]QNB binding varied with a wide range (0.02-2.5mcM). The Pseudo-Hill coefficients for inhibition of [3H]QNB binding by most of H1-blockers examined except for oxomemazine inhibition of [3H]QNB binding were close to one. The inhibition curve for oxomemazine in competition with [3H]QNB was shallow(nH = 0.74) indicating the presence of two receptor populations with different affinities for this drug. The proportion of high and low affinity was 33:67. The Ki values for oxomemazine were 0.045 +/- 0.016mcM for high affinity and 1.145+/-0.232mcM for low affinity sites. These data indicate that muscarinic receptor blocking potency of H1-blockers varies widely between different drugs and that most of H1-blockers examined are nonselective antagonist for the muscarinic receptor subtypes, whereas oxomemazine might be capable of distinguishing between subclasses of muscarinic receptor.

닭에서 Ethambutol이 탄수화물대사에 미치는 영향

이신웅 ( Shin Woong Lee ),박정하 ( Jeung Ha Bak ),조규박 ( Kyu Park Cho ),심운택 ( Un Taek Shim ) 대한결핵 및 호흡기학회 1978 Tuberculosis and Respiratory Diseases Vol.25 No.3

디벤아민에 의한 무스카린 수용체 아형의 불활성화

이신웅(Shin Woong Lee),장태수(Tae Soo Jang) 대한약학회 1995 약학회지 Vol.39 No.6

Dibenamine inhibited [3H]quinuclidinyl benzilate ([3H]QNB) binding in both concentration and incubation time-dependent manners. The IC50 value of dibenamine for the inhibition of the specific binding of 100pM [3H]QNB following incubation of cerebral microsomes with dibenamine at 37oC for 15 min was 20mcM. Dibenamine irreversibly decreased the binding site concentration for [3H]QNB binding without affecting the affinity of [3H]QNB for the muscarinic receptor. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsomes indicated the presence of two receptor subtypes with high (M1 receptor, Ki=5nM) and low (M2 receptor. Ki=l6OnM) affinity for pirenzepine. However, dibenamine(20mcM) treatment under the condition employed in these experiments caused steepening of the pirenzepine competition curve. The Ki value for pirenzepine in dibenamine treated microsomes was approximately 120nM, suggesting a selective decrease in the number of Ml receptor. Although dibenamine also inhibited [3H]QNB binding to ventricular microsomes with the IC50 value of 120mcM, the sensitivity for dibenamine in the ventricle was much lower than that in the cerebrum. These results indicate that dibenamine at low concentrations selectively inactivates the muscarinic M1 receptor.

항 히스타민제의 H1 수용체와 무스카린 수용체에 대한 상대적 역가

이신웅(Shin Woong Lee),박영주(Young Joo Park),이정수(Jeung Soo Lee) 대한약학회 1993 약학회지 Vol.37 No.4

The muscarinic antagonist l-[benzilic-4,4''-3H]quinuclidinyl benzilate([3H]QNB) bound to a single class of muscarinic receptor with high affinity in guinea pig ileal membranes. The KD and Bmax values for [3H]QNB calculated from analysis of saturation isotherms were 54pM and 156fmol/mg, respectively. H1-blockers inhibited [3H]QNB binding to ileal membranes with Ki values ranged from 0.008gM to 1.6mcM. The pseudo-Hill coefficients of HI-blockers for inhibition of [3H]QNB binding to the ileal membranes were close to unit. The Ki values for H1-blockers were similar to the Km values calculated by Schild plot of functional data obtained from inhibition of the carbachol-induced contraction in guinea-pig ileum, suggesting that binding of HI-blockers vs [3H]QNB in ileal membranes represents an interaction with a receptor of physiological relevance. The KH values of H1-blockers for H1-receptor estimated from inhibition of the histamine-induced contraction were the range of 0.15nM to 56.5nM. The KM/KH ratio of Hi-blockers varied over a wide range of 3 to 2300. Thus, the antihistaminic potencies of H1-blockers do not correlate with their antimuscarinic potencies, which suggest that antihistamines have different antimuscarinic potencies in therapeutic blood levels causing similar antiallergic effect. Among 13 traditional antihistaminics examined in this study, drug having the highest and the lowest KM/KH ratio is triprolidine and diphenidol, respectively. The present results demonstrate that the antimuscarinic property of antihistamines is not necessary for their antiallergic effect, and data on the affinity of antihistamines for musrinic and H1-receptors can be an important parameter in the selection and evaluation of these drugs.

항 Histamine제와 Muscarinic Recepter와의 상호작용(I) 심장 muscarinic recepter에 대한 작용

이신웅(Shin Woong Lee),박영주(Yeung Joo Park),이정수(Jeong Soo Lee),하광원(Kwang Wan Ha),진갑덕(Kap Duck Jin) 대한약학회 1988 약학회지 Vol.32 No.2

[3H] Quinuelidinyl benzilate(QNB) binding assays were performed in the dog ventricular sarcolemma fraction enriched approx. 32-fold in sarcolemma compared to the starting homogenate to elucidate the effect of antihistaminics on cardiac muscarinic receptor. Chlorpheniramine(CHP) inhibited specific binding of [3H]QNB and delayed the equilibrium binding. The rate constants at 37oC for formation and dissociation of the QNB receptor complex were 0.38 X 1O9M-1min-1 and 1.6 X 1O-2min-1, respectively. The mean value for the dissociation constant from the pairs of the rate constants was 43.2pM and this value was similar to the value(44.8pM) determined from Scatchard analysis. CHP decreased association rate constant, indicating increase in KD value. Decrease in affinity without affecting the binding site concentration(Bmax) for [3H]QNB binding by CHP was also demonstrated by Scatchard analysis. Ki values for H1-blockers that inhibited specific [3H]QNB binding were 0.02-4.8mcM. Cimetidine with Ki value of 230mcM, however, was ineffective in displacing [3H]QNB binding at concentration of 50mcM. The Hill coefficient for H1-blockers were about one. The results indicate that H1-antihistaminics inhibit [3H]QNB binding by interaction with myocardiac muscarinic cholinergic recepter and anticholinergic side effects of these drugs are mainly due to this recepter blocking mechanism.

인삼 Saponin 이 양신장에서 정제한 Na+, K+-ATPase 의 활성 염산화 및 [3H] Ouabain 결합에 미치는 영향

이신웅(Shin Woong Lee),전갑득(Kap Duck Jin),이정수(Jeung Soo Lee) 영남대학교 자원문제연구소 1986 資源問題硏究 Vol.5 No.-

개 심실 형질막의 분리 및 그 방향성에 관한 연구

이신웅(Shin Woong Lee),이정수(Jeung Soo Lee),구정옥(Jeoung Ok Ku) 영남대학교 자원문제연구소 1987 資源問題硏究 Vol.6 No.-