• Preventive Nutrition and Food Science
• /
• v.5 no.2
• /
• pp.75-80
• /
• 2000

To separate ACE inhibitors from edible plants, spices, and herbs, 285 extracts of 95 sources were screened for ACE inhibitory activity. The extract of Sinapis alba L. had the most potent ACE inhibitory activity. Mustard seeds were crushed homogeneously and extracted with hexane and water successively. Lyophilized water extract was fractionated with $H_2O$:butanol(1:1). The ACE inhibitor was purified from butanol fraction by methanol precipi-tation, gel filtration, HPLC, and FPLC with Superdex peptide HQ 10/30 column. The active fraction has been purified to homogeneity, which was proven by gel filtration using FPLC system. The yield was 0.02%. The com-pound has a molecular weight of about 640. The compound competitively inhibited ACE activity and the $IC_{50}$ value was 79$\mu\textrm{g}$/ml. The purified compound showed uterus contraction activity in isolated rat uterus.

• Korean Journal of Pharmacognosy
• /
• v.15 no.1
• /
• pp.6-14
• /
• 1984

Pharmacological studies have been carried out with the methanol extract of the whole plant of Pseudostellaria palibiniana Ohwi (Caryophyllaceae). The results showed that it had stimulation effect on heart, hypotensive actions depending on extract contents, stimulation effect on respiration, contraction on excised intestines, enhancement of tension on excised uterus, antineoplastic activity on Ehrlich carcinoma, liver protective activity against $CCl_4$ intoxication, writhing and diuretic activities.

• The Korean Journal of Physiology
• /
• v.17 no.2
• /
• pp.103-107
• /
• 1983

This experiment was undertaken to see whether dopamine has any effect on a uterine function and whether the uterus has a dopamine receptor. We used 14 female rats in the diestrus state which was identified by a vaginal smear. Under ether anesthesia, 3 pieces(1 cm length) from each side of the uterus were dissected out and mounted in 3 tissue chambers (4 cm diameter, 10 cm height) that contained Krebs-Ringer solution. The solution was continuously aerated with 95% $O_2$ containing 5% $CO_2$ and kept $37^{\circ}C$ consistantly during the whole experimental period. The spontaneous contractile activity of the isolated uterus was recorded using a force transducer. After a recovery period of 15 min in the chamber, the following experiments were carried out. In 7 rats, each piece of the uterus was received dopamine at concentrations of $10^{-4}$, $10^{-5}$ or $10^{-6}\;M$ for 10 min and then followed by domperidone at a concentration of $10^{-5}\;M$. In another 7 rats, each piece was received domperidone, a specific peripheral dopamine receptor antagonist, was administered at a concentration of $10^{-5}\;M$ for 5 min prior to dopamine at concentrations of $10^{-4}$, $10^{-5}$, or $10^{-6}\;M$. Dopamine inhibited the spontaneous uterine contraction dose-dependently (r=0.99, p<.01). The inhibited contractility by dopomine was significantly (P<.05) resumed by post-treatment of domperidone. Pre-treatment of domperidone also blocked significantly(p<.05) the inhibitory effect of dopamine. It is concluded from these results that dopamine has inhibitory role upon the spontaneous uterine contraction of the rat in the diestrus state and domperidone antagonized the inhibitory effect of dopamine. These results suggest strongly that dopamine may exert the inhibitory effect via the dopamine receptor in the rat uterus.

• Journal of Pharmaceutical Investigation
• /
• v.12 no.3
• /
• pp.93-99
• /
• 1982

The effects of erythrosine on motility of frog heart, rabbit duodenum and uterus isolated, and on mice intestinal motility and voluntary activity were investigated. The effect of erythrosine $2.3{\times}10^{-5}M$ on isolated frog heart showed a slight decrease of the amplitude of motility, and the heart motility stopped in $3.5{\times}10^{-4}M$. With the administration of erythrosine $3.4{\times}10^{-4}M$, the isolated rabbit duodenum showed a remarkable contraction and this effect was inhibited by atropine $1.4{\times}10^{-7}M$. The administration of erythrosine $2.3{\times}10^{-3}M$, produced a contractile effect on the isolated rabbit uterus, and the motility of $6.9{\times}10^{-3}M$ started to increase in contractions at first and finally stopped, keeping in continuous contractions. The effects of erythrosine 0.5, 1.0, 10, and 20mg/kg on mice intestinal motility were not significantly different from this of the normal control. With 20 and 40mg/kg of erythrosine, the effects on voluntary activity showed the decrease of 21 and 58% respectively, and voluntary activity of the mice pretreated with erythrosine 20 and 40mg/kg, induced by C. N. B. 30mg/kg showed the decrease of 57 and 78% respectively in contrast with the normal control group.

• Korean Journal of Veterinary Research
• /
• v.36 no.1
• /
• pp.83-91
• /
• 1996

Activation of $K^+$ channels induces relaxation of smooth muscles by reducing electrical excitability and cytosolic free $Ca^{2+}$ level. ${\beta}$-adrenergic agonist isoproterenol is known to induce relaxation of the uterine smooth muscle by membrane hyperpolarization and $K^+$ efflux. Recently it is suggested that the activity of $Ca^{2+}$-activated $K^+$ channel was increased by isoproterenol in the uterine myocytes isolated from myometrium of the pregnant rat. However, the type of $K^+$ channel mediating the relaxant effect of isopreterenol in the tissue level has not yet studied. In this work, we investigated the type of $K^+$ channels involved in the isoproterenol-induced relaxation of uterine smooth muscle by measuring the integrated insometric tension of the estrogen-treated isolated nonpregnant rat uterus. Contraction of uterine tissue was induced by oxytocin (0.2nM, 2~3 contractions/min) or high KCl(20~80mM). The result are as follows : 1. Isoproterenol($10^{-10}{\sim}10^{-4}M$) inhibited oxytocin-induced contraction of isolated rat uterus($EC_{50}=1.17{\times}10^{-10}M$). 2. Isoproterenol($10^{-10}{\sim}10^{-4}M$) effectively inhibited uterine contraction induced by low KCl(20~40mM) but little those induced by high KCl(60~80mM). 3. Relaxant effect of isoproterenol($10^{-10}{\sim}10^{-4}M$) on 0.2nM oxytocin-induced contraction was effectively reduced by 4-aminopyridine(3, 10mM) but little by TEA(10~30mM), $Ba^{2+}$($1{\sim}30{\mu}M$) and glibenclamide($100{\mu}M$). Our data suggest that the relaxant effect of isoproterenol is mediated by the $K^+$ channel(s) which can be blocked by 4-aminopyridine.

• Journal of Pharmaceutical Investigation
• /
• v.14 no.2
• /
• pp.86-91
• /
• 1984

A ginseng preparation (GP) consisting of ginseng ex., lycium fructus ex., four kinds of vitamines and caffein was evaluated for acute toxicity and general pharmacology. Average lethal doses $(LD_{50})$ of GP in male mice were 2,988mg/kg (i.p.) and more than 3g/kg (p.o.). In dosage of 300 and 900mg/kg (p.o.) showed no analgesic activity in both tests of the writhing method induced by acetic acid and of tail pressure method and no effect on the pentetrazole-induced convulsion. However, it appeared to have a hypothermic action only in dose of 900mg/kg. The duration of hypnosis induced by hexobarbital sodium in mice was shortened by GP, being probably due to caffein. GP Produced no marked contraction of isolated ileum and uterus in high concentrations of up to $1{\pm}10^{-3}g/ml$. These results suggested that GP did not show any considerable central nervous depressant activity and exhibited very weak actue toxicity in mice.

• Korean Journal of Animal Reproduction
• /
• v.19 no.4
• /
• pp.245-250
• /
• 1996

This study was undertaken to illustrate the uterotonic effect of Leonurus sibiricus. It was dissolved in sterile water and several different dosages were administered both in vitro and in vivo study. Rat uterine tissue for in vitro bioassay was obtained from estrous rat. From the low to high dosages of Leonurus sibiricus were tried and each uterine contraction was recorded and integrated. Anesthetized estrous rat for in vivo study was cannulated into the jugular vein for infusion of the compound. Another cannula with a balloon tipped and water filled was inserted into the uterus to measure uterine activity. While the uterine tissue did not respond to low dosage of compound, high dosage of compound stimulated the tissue to contract less than 1 minute with low amplitude. In vivo rat uterus showed a certain, consistent pattern of contractions which was initial relaxation and followed by prolonged and increased amplitude of contractions. It also caused a short breathing stop which might be due to acute acidosis.

• The Korean Journal of Physiology
• /
• v.18 no.1
• /
• pp.37-50
• /
• 1984

The effects of $Ca^{++}$ and its antagonists (verapamil and $La^{+++}$) upon the spontaneous contraction and the contracture induced by 60 mM K-Tyrode solution were studied in the isolated uterine muscle. Longitudinal muscle strips were prepared from the rat uteri at estrous stage. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at 35^{\circ}$. The results obtained were as follows: 1) In the uterine strips contracting spontaneously, both the amplitude of peak tension and the area of contraction curve increased dose-dependently in the range of $0.5${\sim}8$ mM $Ca^{++}$. The frequency of contraction increased as the concentration of $Ca^{++}$ increased up to 2 mM, but above this concentration the frequency decreased. In $Ca^{++}-free$ media, however, contraction did not develop. In the contracture induced by 60 mM K-Tyrode solution, the developed tension increased dose-dependently as the concentration of external $Ca^{++}$ increased to 8 mM. In the absence of external $Ca^{++}$ K-contracture appeared, but it was not sustained. 2) The spontaneous contraction of rat uterus was suppressed by verapamil in proportion to an increase of its concentration and totally abolished at the concentration of $3{\times}10^{-4}\;g/l$, but the spontaneous contraction re-appeared by addition of $Ca^{++}$. The amplitude of peak tension recovered completely but the recovery of frequency was incomplete. K-contracture decreased in a dose-dependent manner after the treatment with verapamil and totally disappeared at its concentration of $3{\times}10^{-4}\;g/l$. Even in this case contracture developed again by extra $Ca^{++}$. 3) The spontaneous contractile activity was inhibited by $La^{+++}$. At the concentration of $10^{-4}$M $La^{+++}$, fibrillation appeared. In the strip inhibited by $10^{-5}M\;La^{+++}$, contractility recovered completely by extra $Ca^{++}$ while in the $10^{-4}M\;La^{+++}$ treated preparation, the rhythmic spontaneous contraction did not develop even at the concentration of 16 mM $Ca^{++}$. After the initial transient depression of contracture tension by $10^{-3}M$ of $La^{+++}$, the strip stowed considerably large size of contracture, hardly influenced by external $Ca^{++}$ or verapamil. The results obtained in this experiment suggest that in the rat uterine muscle there would be some competitive actions between $Ca^{++}$ and its antagonists. It is speculated that $Ca^{++}$ plays an important role in the conduction of excitation, and $La^{+++}$ influences upon cellular $Ca^{++}$ mobilization and re-uptake process as well as transmembrane $Ca^{++}$ transport in a K-depolarized state.

• Korean Journal of Veterinary Research
• /
• v.22 no.1
• /
• pp.1-8
• /
• 1982

The effect of acetylcholine, oxytocin and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) on cyclic nucleotide levels in estrogen-primed rabbit whole uterus were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiestrase inhibitor, and indomethacin, a prostagandin inhibitor. In the absence of MIX, acetylcholine increased guanosine 3', 5'-cyclic monophosphate (cGMP), but had no effect on adenosine 3', 5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin had no influence on cGMP, but decreased cAMP levels. $PGF_{2{\alpha}}$ increased cGMP and decreased cAMP levels. MIX increased both cAMP and cGMP levels. Oxytocin and $PGF_{2{\alpha}}$ further increased cGMP levels, indicating activation of guanylate cyclase activity. The ratio of cAMP/cGMP was decreased by uterine stinulants both in presence and absence of MIX. Indomethacin elevated cAMP and cGMP revels. The effects of uterine stimulants in the presence of indomethacin on cyclic nucleotide levels were varied from tissue to tisse. In general, oxytocin decreased cGMP and $PGF_{2{\alpha}}$ increased cAMP/cGMP levels, but the effects were statisically nonsignicficant. The cAMP/cGMP ratio was increased by uterine stimulant in the presence of indomethacin. In conclusion, uterine stimulants eased cAMP/cGMP ratio which indicates that the uterine stimulants have opposing effects on adenylate cyclase and guanylate cyclase activities. The endometrium plays a role in the regulation of cyclic nucleotide levels and uterine contraction by means of PG synthesis. Indomethacin has an unknown activities besides both of PG synthetase and phosphodiesterase inhibitions.

• Archives of Pharmacal Research
• /
• v.23 no.1
• /
• pp.72-78
• /
• 2000

The general pharmacological properties of YJA20379-1 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]benzoimidazole, a novel proton pump inhibitor with antiulcer activities were investigated in mice, rats, guinea pigs and rabbits. YJA20379-2 at oral doses of 50, 100 and 200 mg/kg did not affect the general behaviour, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic or anticonvulsant action at 200 mg/kg. Locomotor activity and body temperature were not influenced at 100 mg/kg. At a concentration up to 2{\times}10^{-4} g/ml$, YJA20379-2 did not produce any contraction or relaxation of isolated preparations, such as the rat fundus, the guinea pig ileum and the rat uterus, and did not antagonize the contractile response to several spasmogens, such as histamine, acetylcholine, serotonin and oxytocin. At dosages up to 200 mg/kg p.o. YJA20379-2 did not affect the pupil size of mice. Intestinal propulsion of mice was not affected up to 200 mg/kg p.o. and the drug did not affect urinary excretion at 100 mg/kg p.o. These results indicate that at dosages up to 100 gm/kg p.o. YJA20379-2 was found not to affect this pharmacological profile. However, at 200 mg/kg the drug lowered body temperature and showed decreased in locomotor activity and urine volume.