• Journal of Yeungnam Medical Science
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• 제6권2호
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• pp.13-22
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• 1989

Benzodiazepine 계통의 약물들은 진정, 최면제로 진정, 최면, 불안의 감소와 함께 횡문근 이완과 항 경련 작용을 가진다는 것은 이미 잘 알려진 바이나 이러한 약리 작용의 기전에 대해서는 아직 확실하게 밝혀진 바가 없다. 최근 이러한 약리 작용과 연관성을 지니는 것으로 알려진 뇌내의 benzodiazepine의 수용체(receptor)를 통한 자극 전달 기전에 calcium 이온의 역할이 큰 비중을 차지할 수 있음이 대두되었다. 또 뇌 이외의 다수의 말초 조직에서도 benzodiazepine의 수용체가 있으며, 이들도 calcium 이온과 상호 작용 할 것이라고 보고된 바가 있으나 이들의 약리 작용과 그 작용 기전에 대해서는 아직 확실히 밝혀진 바가 없다. 이에 저자는 benzodiazepine 계통 약물 중 대표적이라 할 수 있는 diazepam을 사용하여 diazepam이 장관 평활근의 수축성에 미치는 영향을 calcium 이온과 연관시켜 검색하기 위하여 흰쥐 회장 평활근에서 적출한 종주근 절편을 적출 근편 실험조내에서 diazepam 처치 전후의 carbachol, histamine 및 calcium 유발 수축성의 변화를 등척성 장력 측정기를 사용하여 관찰하여 다음과 같은 결과를 얻었다. 1. Diazepam은 흰쥐 회장 절편의 기본 장력을 농도 의존적으로 감소시켰다. 2. Diazepam은 흰쥐 회장 절편의 carbachol-유발 수축 작용을 고농도에서는 억제시켰으며 저농도에서는 오히려 증강시키는 이중 효과를 나타내었다. 3. Diazepam 존재하에서 흰쥐 회장 절편의 histamine-유발 수축 작용은 억제되었으며, diazepam의 농도가 증가함에 따라 그 억제도는 증가하였다. 4. 칼슘 배제 용액에서 칼슘 재 투여로 인한 회장 절편의 장력의 회복율은 diazepam 전처치에 의해 억제되었으며, diazepam의 농도가 증가함에 따라 그 억제도는 증가하였다. 이상의 실험 결과로 미루어 diazepam은 흰쥐 회장 종주근의 수축성을 억제시키며 이 작용은 diazepam이 평활근 세포내로의 calcium의 유입을 억제함으로써 나타나는 것으로 사료된다.

• 약학회지
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• 제37권6호
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• pp.625-630
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• 1993

Among the six antihistamine agents tested in this study, homochlorcyclizine showed the highest bradykinin antagonistic activity in the receptor binding assay as well as the isolated rat ileum assay. Schild plot analysis of bradykinin-induced ileal contraction in the presence of three different concentrations of homochlorcyclizine revealed a pA$_{2}$=6.26, and a correlation coefficient of 0.984. Homochlorcyclizine of (100 $\mu{M}$ final concentration) also showed 25% antagonistic activity in the receptor binding assay.

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.170-177
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• 1999

PEG-hemoglobin SB1 (SB1), which is a hemoglobin-based oxygen carrier, is intended to use as a safe blood substitute against brain ischemia and stroke. The general pharmacological profiles of SB1 were studied. The doses given were 0, 5, 10, 20 ml/kg and drugs were administered intravenously. The animals used for this study were mouse, rat and guinea pig. SB1 showed no effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital sleeping time, anticonvulsant activity, analgesic activity, blood pressure and heart rate, left ventricular peak systolic pressure, left ventricular end diastolic pressure, left ventricular developing pressure, double product, heart rate, coronary flow rate, smooth muscle contraction using guinea pig ileum, gastrointestinal transport, gastric secretion, urinary volume and electrolyte excretion at all doses tested except the decrease of body temperature. These findings demonstrated that SB1 possesses no general pharmacological effects at all doses tested.

• Biomolecules & Therapeutics
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• 제10권4호
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• pp.258-267
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• 2002

In this study the general pharmacological profiles of AS6 on the central nervous system, cardiovascular and the other organs were investigated. The dosages given were 0, 250, 500 and 1000 mg/kg and drugs were orally administered. The animals used for this study were mice, rats and guinea pigs. Significant increases (p<0.01) in the charcoal transport capacity were observed at the high dose of 1000 mg/kg and significant increases in retardation of pain threshold were observed in the test using acetic acid in all dosed animals. However, AS6 showed no noticeable effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital-induced sleep time, body temperature, analgesic activity in the test using hot plate method and anticonvulsant activity. Furthermore no noticeable effects were observed in cardiovascular functions in the isolated rat heart, contraction and relaxation of the smooth muscle in the isolated guinea ileum, gastric secretion and renal function.

• 대한약리학회지
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• 제24권1호
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• pp.103-109
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• 1988

Buxus microphylla var. koreana Nakai에 존재 하는 steroidal alkaloid인 cyclobuxine D는 흰쥐에 있어 심박동수 감소 작용, 적출 개구리 심장에서 수축력 감소작용, 토끼 적출 장관에서 acetylcholine과 $Ba^{++}$.에 유발되는 수축에 대한 억제작용 등을 나타낸다고 보고되었다. 본 연구에서는 흰쥐 적출 자궁에서 acetylcholine, oxytocin과 $Ba^{++}$에서 의해 나타나는 수축 작용에 대한 cyclobuxine D의 영향을 관찰하였으며, 또 흰쥐 적출장관에서 칼륨에 의해 활성화되는 칼슘채널에 대한 cyclobuxine D의 작용을 관찰하였다. Cyclobuxine D는 흰쥐 적출 자궁에서 acetylcholine, oxytocin과 $Ba^{++}$에 의해 증가되는 peak tension과 duration을 용량적으로 현저히 억제하였다. Cyclobuxine D는 oxytocin보다 acetylcholine에 의해 나타나는 수축작용에 대해 강하게 작용했다. 흰쥐 적출 장관(ileum)을 Ca을 고갈시킨 Tyrode's 용액에 $40{\sim}50$분 담그고 $Na^+$ 대신 $K^+$로 대체시킨 용액에 10분간 담근 후 1.8 mM $CaCl_2$를 가했을 때 이중적인 근육수축작용이 나타난다(Phasic and tonic increase in tension). Cyclobuxine D $(6.2{\times}10^{-5}\;M)$은 이 두 components를 유의하게 억제하였으며 tonic component가 최대치에 도달했을 때 cyclobuxine D $(3.1{\times}10^{-4}\;M)$을 가하면 근육은 긴장도를 빨리 상실했다. 이 결과는 적출 장관에 있어 칼륨에 의해 활성화되는 칼슘 채널이 cyclobuxine D에 의해 차단되고 있음을 나타낸다. 이상의 결과에서 cyclobuxine D의 흰쥐 적출 자궁에 대한 수축 억제 작용은 voltage-dependent calcium channel 차단에 밀접한 관련이 있는 것으로 사려된다.

• 대한수의학회지
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• 제42권2호
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• pp.283-288
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• 2002

The present study was carried out to examine the effect of insulin formula on blood glucose change in normal Sprague-Dawley male rats. Also, this study was performed to investigate the feasibility of oral insulin formula development. To administrate the insulin formula into intestine, the surgical technique, celiotomy, was performed in rats. Insulin formula was administrated at a dose of 24.5 IU/kg via duodenum, ileum, and colon of the rats, and the blood glucose level was measured. For the comparison, the vehicle without insulin was administrated into ileum via celiotomy. Also, this insulin formula was administrated into rats orally using sonde and the same parameter was treasured. The bloods of all groups were collected from tail veins using syringes at given time interval. Orally administrated group did not show the change of blood glucose level and control group slightly show the change of blood glucose level at 1 hour after celiotomy. All intestinally administrated groups showed the change of blood glucose level. Among the tested groups, ileac administration group and colonic administration group showed the significant change of blood glucose level. Particularly, ileac administration group showed the lowest blood glucose level. To calculate the bioavailability of intestinal and oral administration, insulin solution was injected subcutaneosly, common insulin injection route, into another normal rats. The bioavailability of ileac group was 8.3% when compared with subcutaneous injection, duodenal group was 1.8%, colonic group was 4.2%, and oral group was 0.2%, respectively.

• 약학회지
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• 제40권5호
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• pp.591-598
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• 1996

The water extracts of ten crude drugs were tested for the spasmolytic and anti-peptic ulcer activities on rat ileum smooth muscle contraction and aspirin-induced acute hemorrhag ic erosive gastritis respectively. The water extract of Aurantii immaturi pericarpium(AIP)($IC_{50}=1.5{\times}1O^{-2}$g/l), Aurantii nobilis pericarpium(ANP)($IC_{50}=2.5{\times}1O^{-2}$g/l), Cyperi rhizoma(CR)($IC_{50}=3.3{\times}1O^{-2}$g/l). Linderae radix(LR) ($IC_{50}=6.8{\times}1O^{-2}$), Aurantii fructus immaturus(AFI)($IC_{50}=11.8{\times}1O^{-2}$), Saussureae radix(SR)($IC_{50}=13.2{\times}1O^{-2}$g/l) and Ponciri fructus(PF)($IC_{50}=23.3{\times}1O^{-2}$g/l) showed inhibitory activity on the isometric contraction of rat ileum smooth muscle induced by electrical stimulation in a concentration-dependent manner, whereas the water extracts of Arecae pericarpium(AP), Agastachis herba(AH) and Magnoliae cortex(MC) potentiated the isometric contraction. In the aspirin-induced acute gastritis, the water extracts of MC, AP and CR reduced significantly the gastric juice secretion, gastric juice acidity and pepsin activity. They also showed protective activity of gastric mucosal layer from erosion and petichial hemorrhage in gross and histological examination.

• Journal of Pharmaceutical Investigation
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• 제21권4호
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• pp.215-222
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• 1991

The absorption characteristics of itraconazole, which is an antifungal agent, from intestinal segments in the anesthetized rat i1l situ were investigated in order to design an effective oral drug delivery system. The pH-solubility profile of itraconazole, the rate and extent of absorption of itraconazole, the optimal absorption site(s) of itraconazole and the absorption enhancing effect of sodium cholate on itraconazole were examined in the present study. In situ single-pass perfusion method and recirculating perfusion technique using duodenum(D), jejunum(J) and ileum(I) were employed for the calculation of apparent permeability(Pe) and apparent first-order rate constant(Kobs). respectively. The results of this study were as follows; (1) Itraconazole showed appreciable aqueous solubility only at pH values of below 2.0. (2) pe(cm/sec) decreased in the following order: $D(10.24{\pm}1.78{\times}10^{-4})>J(8.86{\pm}0.79{\times}10^{-4})>I(3.78{\pm}0.13 X 10^{-4})$. (3) $Kobs(min^{-1})$ decreased in the following order: $J(17.12{\pm}3.19{\times}10^{-3})>D(13.37{\pm}0.6{\times}10^{-3})>I(11.05{\pm}0.91{\times}10^{-3})$. (4) The solubility of itraconazole markedly increased with the increase of the concentration of sodium cholate. (5) The addition of 10 mM sodium cholate significantly increased the apparent first-order rate constant of itraconazole in the ileum by a factor of 6.8.

• 동의생리병리학회지
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• 제20권4호
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• pp.924-928
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• 2006

This study was undertaken to determine the effects of Zusanli(ST 36) electro-acupuncture(EA) on the small intestinal motility in rat. The motor activity of the rat small intestine was evaluated by intestinal transfortation rate. Changes in the motility in vivo of ileum was measured before and 10 minutes after acupuncture. In order to examine whether EA effect was affected by stimulated duration and left or right sides of ST36 acupoint, both of the difference effects of left or right sides on acupoints of ST 36 and the stimulated duration of 10, 20, 30 min. were investigated on the motility in vivo of ileum. These results suggest that effect of Zusanli(ST36) for increasing the small intestinal motility should stimulate more than 20 minutes, left ST36 EA has stronger effect than right ST36 EA.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.442-447
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• 2010

This study was conducted to determine whether treatment with the anti-inflammatory eupatilin influences intestinal smooth muscle contraction stimulated by carbachol and, if so, to investigate the related mechanism. Denuded ileal or colonic muscles from Sprague-Dawley rats were used for the study and measurements of isometric contractions were obtained using a computerized data acquisition system; this data was also combined with results from molecular experiments. Eupatilin from Artemisia asiatica Nakai significantly decreased carbachol-induced contractions in both ileal and colonic muscles. Interestingly, eupatilin decreased carbachol-induced phosphorylation of ERK1/2 more significantly than that of MYPT1 at Thr855 in ileal and colonic muscles. However, eupatilin significantly decreased phosphorylation of MYPT1 at Thr855, but only in ileal muscle. Therefore, thin filament regulation, including MEK inactivation and related phospho-ERK1/2 decrease, is mainly involved in the eupatilin-induced decrease of intestinal contraction induced by carbachol. In conclusion, this study provides the evidence and a possible related mechanism concerning the inhibitory effect of the flavonoid as an antispasmodic on the agonist-induced contractions in rat ileum and colonic muscles.