• 대한약리학회지
• /
• 제24권1호
• /
• pp.31-42
• /
• 1988

본 연구에서 한국산 인삼의 활성성분의 하나인 Panaxadiol(PD)에 대한 가토적출부신에서 카테콜아민(CA)의 분비작용과 작용기전을 파악하고자 실험을 시행하여 다음과 같은 결과를 얻었다. $PD(400{\mu}g)$을 가토적출부신에 투여하였을 때 카테콜아민의 분비를 의의있게 증가시켰다. PD의 이러한 CA 분비작용은 atropine 처치로 현저히 억제되었다. Physostigmine 전처치시 PD 뿐만 아니라 Ach의 CA 분비작용은 뚜렷이 증가되었다. 그러나 chlorisondamine 전처치로 PD나 Ach의 분비 효과는 억제되었다. 또한 $PD(400{\mu}g/30\;min)$을 주입한 후에 Ach의 CA 분비 효과는 오히려 강화되었다. PD나 Ach의 작용은 adenosine 전처러시 현저히 증강되었다. EGTA(5mM)와 함께 Ca-free Krebs액으로 30분 주입한 경우에 Ach의 분비작용은 거의 전적으로 차단되었으며, PD의 작용도 약화되었다. 이상의 실험결과로 보아, PD는 가토적출부신에서 $Ca^{++}$ 의존적으로 CA분비를 증가시키며, 이러한 작용은 cholinergi muscarinic 및 nicotinic receptor의 흥분작용에 기인하며, chromaffincell 대한 일부 직접작용도 개재되어 나타나는 것으로 사료된다.

• 대한약리학회지
• /
• 제24권2호
• /
• pp.179-187
• /
• 1988

소듐에 의한 칼슘의 유리는 verapamil, TTX, TEA의 영향을 받지 않았다. $100\;{\mu}M\;Cd6{++}$과 $Zn^{++}$은 소듐에 의한 칼슘 유출을 유의하게 억제하였다. $Cd^{++}$은 $Ki\;100\;{\mu}M\;Cd6{++}$로써 비상경적으로 소듐-칼슘 교환이동을 억제하였다. $Cd^{++}$은 SH기의 산화를 초래하였으나, $Zn^{++}$은 거의 영향을 나타내지 않았다. $Cd^{++}$과 $Zn^{++}$은 $Na^+-Ca^{++}$ ATPase를 효과적으로 억제하였으나 $Ca^{++}-Mg^{++}$ ATPase를 약간 억제시켰다. Carbonyl cyanide chlorophenylhydrazone, 2,4-dinitrophenol과 sodium arsenate는 소듐에 의한 칼슘 유리를 촉진하였다. Dibucaine과 oligomycin은 소듐에 의한 칼슘의 유리를 약간 억제하였으나, 이에 반하여 ouabain은 약간 촉진하였다. 이상의 실험 결과로부터 신경 세포막에서의 소듐-칼슘 교환은 이온 통로를 통하여 이루어지지 않을 것으로 시사되었다. 소듐-칼슘 교환이동은 $Cd^{++}$에 민감하게 억제되고 이 이동기전에 synaptosome막의 SH기가 관여할 것으로 사료되었다. 또한 소듐-칼슘 교환은 세포막 단백질 성분의 인산화 반응 동안에 억압될 것으로 추정되었다.

• 동국한의학연구소논문집
• /
• 제1권
• /
• pp.55-80
• /
• 1992

In order to examine that the effect of Sam Hwa San, circulating the vital energy of Sam Cho and controlling body fluid metabolism, gives any influence on renal function, changes in the urine flow, eletrolytes excretion, plasma aldosterone concentration and renin activity were observed after intravenous infusion of the Sam Hwa San extract in rabbit. Also in vitro effect of the herb extract on oxygen consumption in renal cortical slices and ATPase activity in kidney microsomes was measured. The following results were obtained : 1. The urine flow was markedly increased at 10 min after intravenous infusion of the Sam Hwa San extract($0.134{\pm}0.015$ vs. $0.433{\pm}0.046ml/min.kg$), but return ed to normal value after 40 min of infusion. 2. The glomerular filtration rate was significantly increased at 10 min after in travenous infusion of the Sam Hwa San extract, and the renal plasma flow at 10 and 20 min after infusion of the Sam Hwa San extract, following return to normal value. 3. $Na^+$ excretion was significantly increased during 10-40 min after intravenous infusion of the Sam Hwa San extract, although showed the maximal rate at 10-20 min. The fractional $Na^+$ excretion was also increased during 10-40 min. $K^+$ excretion was rapidly increased at 10 min after the intravenous Infusion of the Sam Hwa San extract and then gradually decreased to normal level at 40 min. The fractional $K^+$ excretion was significantly increased during 10-40 min after the intravenous infusion of the Sam Hwa San extract. 4. The plasma aldosterone concentration and renin activity were not altered by the infusion of the Sam Hwa San extract. 5. The ouabain-sensitive oxygen consumption of renal cortical slices was significantly reduced by the Sam Hwa San extract(0.5 and 1.0 vol.%). 6. The Na-K-ATPase activity of renal microsomes was strongly inhibited by the Sam Hwa San extract(0.5 and 1.0 vol.%). These results suggest that the Sam Hwa San causes a strong diuretic effect which results from reduction of Na reabsorption in renal tubule by a direct inhibition of Na-pump and, in part, from all increase in renal blood flow. In clinic, it is considered to obtain the therapeutic effect in body fluid metabolism disharmony to cause the circular disorder of vital energy.

• The Korean Journal of Physiology
• /
• 제26권1호
• /
• pp.55-68
• /
• 1992

The effects of changes in extracellular $Na^+\;and\;Ca^+$ concentration on the membrane potential and contractility were studied in the antral circular muscle of guinea pig stomach in order to elucidate the existence and the nature of $Na^+/Ca^{2+}$ exchange mechanism. All experiments were performed in tris buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C.$ The treatment of $10^{-5}$ ouabain was performed to induce intracellular $Na^+$ loading prior to the start of experiment. The results were as follows: 1. $Na^+$-free Tyrode or high $Ca^{2+}$-Tyrode solution hyperpolarized the membrane potential and induced contracture. The time course of contracture was similar to that of change in membrane potential. 2. The degree of hyperpolarization and the amplitude of contracture decreased in accordance with the increase of extracellular $Na^+$ concentration. 3. $Na^+$-free contracture was developed even after blocking the influence of intrinsic nerves by the pretreatment with atropine, guanethidine and TTX. 4. $Ca^{2+}$-channel blockers(D-600 or $Mn^{2+}$) and the blocker of intracellular $Ca^{2+}$ release from sarcoplasmic reticulum(ryanodine) did not suppress the development of $Na^+$-free contracture. And also, dinitrophenol had no effect on $Na^+$-free contracture. 5. Dose-response relationship between extracellular $Na^+$ concentrations and the magnitude of contractures showed a sigmoid pattern. The slope of straight line from Hill plot was 2.7. 6. In parallel with the increase of extracellular $Ca^{2+}$ concentration, the amplitude of contracture increased dose dependently and was maximum at 8 mM $Ca^{2+}$-Tyrode solution. 7. The relationship between extracellular $Ca^{2+}$ concentrations and the magnitude of contractures showed hyperbolic pattern. The slope of straight line from Hill plot was 1.1. From the above results, it is suggested that $Na^+/Ca^{2+}$ exchange mechanism exists in the antral circular muscle of guinea pig stomach and this mechanism affects the membrane potential electrogenically.

• Applied Microscopy
• /
• 제19권2호
• /
• pp.119-137
• /
• 1989

Turtle bladder의 상피조직(上皮組織)과 세포막(細胞膜) 투과성(透過性)을 분석하기 위하여 동결절단법(凍結切斷法)을 적용(適用)하여 전자현미경(電子顯微鏡) 관찰을 하였으며 그 결과 다음과 같이 요약(要約)된다. 1. 방광상피(膀胱上皮)의 3가지 주요세포형(主要細胞形)은 granular-cell, ${\alpha}$ 및 ${\beta}$형(形)의 CA-rich cell로서 구분된다. 2. 과립성세포(顆粒性細胞)의 주요기능(主要機能)은 $Na^+$ 재흡수(再吸收)이며, 두 단계(段階)의 수송과정(輸送過程)으로 설명되며 정단세포막(頂端細胞膜)을 통한 $Na^+$의 세포내(細胞內) 확산이동(擴散移動)과 그후 기저막(基底膜)에 위치한 $Na^{+}\;-K^{+}$ 펌프에 의한 능동수송과정(能動輸送過程)이다. 3. ${\alpha}$ 및 ${\beta}$형(形) CA-rich cell은 $Na^+$ 수송(輸送)에 관여하지 않으며, ${\alpha}$형(形)의 CA-cell은 정단세포막(頂端細胞膜)의 proton펌프를 이용하여 proton 분필(分泌)에 관여한다. 또한 ${\beta}$형(形)의 CA-cell는 정단세포막(頂端細胞膜)을 통한 $HCO_{3}^-$ 분필수송(分泌輸送)의 기능을 가지고 있다. 4. 동결절단법(凍結切斷法)의 적용하에 세포막표면(細胞膜表面)의 특성(特性)을 관찰한 바, ${\alpha}$형(形)의 CA-cell의 정단세포막(頂端細胞膜)은 proton펌프를 함유하는 것으로 보이는 intramembrane particle이 다수 관찰되고 있으며, ${\beta}$형(形) CA-cell은 기저세포막(基底細胞膜)에서 이와같은 intramembrane particle이 나타나고 있다. 5. 상술(上述)한 두 type의 CA-cell에서 수송특성(輸送特性)의 차이는 proton 및 $HCO_{3}^-$ 분필수송(分泌輸送)이 서로 반대의 방향으로 일어나는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권1호
• /
• pp.1-10
• /
• 1999

We sought to find out the mechanism of vascular relaxation by extracellular $K^+$ concentration $([K^+]_o)$ in the cerebral resistant arteriole from rabbit. Single cells were isolated from the cerebral resistant arteriole, and using voltage-clamp technique barium-sensitive $K^+$ currents were recorded, and their characteristics were observed. Afterwards, the changes in membrane potential and currents through the membrane caused by the change in $[K^+]_o$ was observed. In the smooth muscle cells of cerebral resistant arteriole, ion currents that are blocked by barium, 4-aminopyridine (4-AP), and tetraethylammonium (TEA) exist. Currents that were blocked by barium showed inward rectification. When the $[K^+]_o$ were 6, 20, 60, and 140 mM, the reversal potentials were $-82.7{\pm}1.0,\;-49.5{\pm}1.86,\;-26{\pm}1.14,\;-5.18{\pm}1.17$ mV, respectively, and these values were almost identical to the calculated $K^+$ equilibrium potential. The inhibition of barium-sensitive inward currents by barium depended on the membrane potential. At the membrane potentials of -140, -100, and -60 mV, $K_d$ values were 0.44, 1.19, and 4.82 ${\mu}M,$ respectively. When $[K^+]_o$ was elevatedfrom 6 mM to 15 mM, membrane potential hyperpolarized to -50 mV from -40 mV. Hyperpolarization by $K^+$ was inhibited by barium but not by ouabain. When the membrane potential was held at resting membrane potential and the $[K^+]_o$ was elevated from 6 mM to 15 mM, outward currents increased; when elevated to 25 mM, inward currents increased. Fixing the membrane potential at resting membrane potential and comparing the barium-sensitive outward currents at $[K^+]_o$ of 6 and 15 mM showed that the barium- sensitive outward current increased at 15 mM $K^+.$ From the above results the following were concluded. Barium-sensitive $K^+$?channel activity increased when $[K^+]_o$ is elevated and this leads to an increase in $K^+-outward$ current. Consequently, the membrane potential hyperpolarizes, leading to the relaxation of resistant arteries, and this is thought to contribute to an increase in the local blood flow of brain.

• The Korean Journal of Physiology
• /
• 제30권1호
• /
• pp.63-76
• /
• 1996

The aim of present study was to characterize phosphate uptake and to investigate the mechanism for the insulin and insulin-like growth factor(IGF) stimulation of phosphate uptake in primary cultured rabbit renal proximal tubule cells. Results were as follows : 1. The primary cultured proximal tubule cells had accumulated $6.68{\pm}0.70$ nmole phosphate/mg protein in the presence of 140 mM NaCl and $2.07{\pm}0.17$ nmole phosphate/mg protein in the presence of 140 mM KCl during a 60 minute uptake period. Raising the concentration of extracellular phosphate to 100 mM$(48.33{\pm}1.76\;pmole/mg\;protein/min)$ induced decrease in phosphate uptake compared with that in control cells maintained in 1 mM phosphate$(190.66{\pm}13.01\;pmole/mg\;protein/min)$. Optimal phosphate uptake was observed at pH 6.5 in the presence of 140 mM NaCl. Phosphate uptake at pH 7.2 and pH 7.9 decreased to $83.06{\pm}5.75%\;and\;74.61{\pm}3.29%$ of that of pH 6.5, respectively. 2. Phosphate uptake was inhibited by iodoacetic acid(IAA) or valinomycin treatment $(62.41{\pm}4.40%\;and\;12.80{\pm}1.64%\;of\;that\;of\;control,\;respectively)$. When IAA and valinomycin were added together, phosphate uptake was inhibited to $8.04{\pm}0.61%$ of that of control. Phosphate uptake by the primary proximal tubule cells was significantly reduced by ouabain treatment$(80.27{\pm}6.96%\;of\;that\;of\;control)$. Inhibition of protein and/or RNA synthesis by either cycloheximide or actinomycin D markedly attenuated phosphate uptake. 3. Extracellular CAMP and phorbol 12-myristate 13 acetate(PMA) decreased phosphate uptake in a dose-dependent manner in all experimental conditions. Treatment of cells with pertussis toxin or cholera toxin inhibited phosphate uptake. cAMP concentration between $10^{-6}\;M\;and\;10^{-4}\;M$ significantly inhibited phosphate uptake. Phosphate uptake was blocked to about 25% of that of control at 100 ng/ml PMA. 3-Isobutyl-1-methyl-xanthine(IBMX) inhibited phosphate uptake. However, in the presence of IBMX, the inhibitory effect of exogenous cAMP was not significantly potentiated. Forskolin decreased phosphate transport. Acetylsalicylic acid did not inhibit phosphate uptake. The 1,2-dioctanoyl-sn-glycorol(DAG) and 1-oleoyl-2-acetyl-sn- glycerol(OAG) showed a inhibitory effect. However, staurosporine had no effect on phosphate uptake. When PMA and staurosporine were treated together, inhibition of phosphate uptake was not observed. In conclusion, phosphate uptake is stimulated by high sodium and low phosphate and pH 6.5 in the culture medium. Membrane potential and intracellular energy levels are also an important factor fer phosphate transport. Insulin and IGF-I stimulate phosphate uptake through a mechanisms that involve do novo protein and/or RNA synthesis and decrease of intracellular cAMP level. Also protein kinase C(PKC) is may play a regulatory role in transducing the insulin and IGF-I signal for phosphate transport in primary cultured proximal tubule cells.

• 대한약리학회지
• /
• 제18권2호
• /
• pp.15-25
• /
• 1982

한국(韓國)에서 빈발(頻發)하는 뇌졸중증(腦卒中症) 환자(患者)의 혈장(血漿)에서 혈전형성(血栓形成)에 관계되는 인자(因子)들을 조사하고, in vitro로 sodium niroprusside의 혈소판(血少板)응집에 대(對)한 작용(作用)을 관찰(觀察)하여 뇌졸중증(腦卒中症) 응급시(應急時) 치료적응용(治療的應用)의 가능성(可能性)을 검토(檢討)하였다. 1) 뇌졸중증(脚卒中症) 환자(患者)의 혈장내(血漿內) 미세혈전형성(微細血栓形成)은 건강인(健康人)에 비(比)하여 유의(有意)하게 (p<0.001) 높았다. 2) 뇌졸중증(腦卒中症) 환자(患者)의 혈장내(血漿內) 과산화지질(過酸化脂質) 및 cathepsin D치(値)는 건강인(健康人)에서 보다 현저히 증가되어 있었다. 3) 건강인(健康人)의 혈소판(血少板)은 1 및 $2{\mu}M\;ADP$에 대(對)하여 2차반응(次反應)에서는 응집률(凝集率)이 감소(減少)된데 반(反)하여 뇌졸중증환자(腦卒中症患者)에서는 응집률(凝集率)이 항진(亢進)되었다. 4) $K^+-free\;PSS$, ouatain, 13-HPLA 및 Cd으로 전처치(前處置)한 소 뇌저동맥(腦底動脈), 토끼 대동맥(大動脈) 및 사람 제대동맥(臍帶動脈)은 혈소판응집률(血少板凝集率)을 증가(增加)시켰다. 그중 $K^+-free$에 처치(處置)한 것이 가장 강(强)하게 작용(作用)하였다. 5) Sodium nitropusside로 전처치(前處置)하였을 때 $K^+-free\;PSS$에 처치(處置)된 혈관(血管)에 의한 항응집반응(向凝集反應)은 용량(用量)에 의존(依存)하여 현저(顯著)히 억제(抑制)되었으며 hydralazine이나 diazoxide에 의하여는 아무런 작용(作用)을 받지 아니하였다. 6) Dibutyryl cyclic AMP 및 8-bromo cyclic GMP 모두 혈소판응집률(血小板凝集率)을 감소시켰고, 후자(後者)는 전자(前者)에 비(比)하여 월등(越等)히 현저(顯著)하였다. sodium nitroprusside에 의한 항응집률(抗凝集率)은 methylene blue 전처치(前處置)에 의하여 길항(拮抗)되었으나, bovine hemoglobin전처치에 의하여는 영향(影響)을 받지 아니하였다. 이상(以上)의 성적(成績)을 종합(綜合)하면, 뇌졸중증(腦卒中症)때, 특히 뇌혈전증(腦血栓症)의 응급치료시(應急治療時) sodium nitroprusside의 응용(應用)이 가능(可能)하다고 사료(思料)되며, 이에 대(對)하여 임상적(臨床的) 치료(治療)가 기대되는 바이다.

• 대한약리학회지
• /
• 제14권1_2호
• /
• pp.1-11
• /
• 1978

가토 심실근에서 추출한 mitochondria에서 $Na^+$ 및 $K^+$이온에 의한 $Ca^{++}$ 유리작용을 관찰하였다. 반응액에 첨가한 1-3mM의 소량 $Na^+$은 mitochondria막에 미리 결합되어있던 $Ca^{++}$을 현저히 유리시켰으며, $K^+$은 단독으로는 $Ca^{++}$ 유리를 유도하지 않았으나 $Na^+$에 의한 $Ca^{++}$ 유리에 대하여는 $Na^+/K^+$비에 따라 그것이 클수록 $Ca^{++}$ 유리를 증가시켰다. 간 및 신장 mitochondria에서도 $Na^+$에 의하 $Ca^{++}$ 유리현상을 보였으나 심근mitochondria에 비하여 $Na^+$에 대한 감수성이 훨씬 미약하여 약 $1/10{\sim}1/5$에 지나지 않았다. 이와같은 mitochondria의 $Ca^{++}$ 유리현상은 비교적 $Na^+$에 특이한 작용이었으며 다른 일가양이온중에서는 $Li^+$에 의해서만 어느 정도 보였다. 부전심근 mitochondria에서의 $Na^+$에 의한 $Ca^{++}$유리는 정상심근 mitochondria에서와 같았으며 이때 digitalis 강심배당체가 직접적으로는 별 영향을 미치지 않았다. 이상에서 심근의 경우 mitochondria는 세포내 $Ca^{++}$을 조절할 수 있는 기구로서 심근수축의 E-C coupling과정에서 세포막의 전기적 흥분현상과 결부하여 $Ca^{++}$을 유리할 수 있을 것으로 추정하였으며, 한편 digitalis배당체의 강심작용기전에 있어서는 digitalis 배당체에 의한 세포막의 $Na^+$, $K^+$-ATPase 억제결과 초래될 수 있는 세포내의 $Na^+$ 증가 및(또는) $K^+$감소가 간접적으로 mitochondria에서부터 $Ca^{++}$ 유리를 증가하여 E-C coupling 과정을 촉진할 수 있을 것을 사료하였다.