• Journal of Veterinary Clinics
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• v.21 no.3
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• pp.291-297
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• 2004

Aminoglycosidic antibiotics have multiple effects on muscle. For example, they have been shown to block L-type $Ca^{2+}$ channels in vascular smooth muscle, cardiac muscle and skeletal muscle. Possibly as a consequence of this effect on $Ca^{2+}$ influx, they have been shown to decrease the contractility of cardiac muscle (gentamicin). The present study evaluated the effects of gentamicin on blood pressure, vasorelaxation and left ventricular pressure. Gentamicin(10, 20, 40mg/kg) produced dose-dependent blood pressure lowering in rat. The pretreatment of MgSO$_4$ and imipramine (Na$^{+}$-Mg$^{2+}$ exchange inhibitor) had no effect in gentamicin-induced hypotension. However, the gentamicin-induced hypotension was significantly potentiated in the preincubation of verapamil or nifedipine (L-type $Ca^{2+}$ channel blockers), and was significantly attenuated by CaCl$_2$ and was slightly attenuated by caffeine (phosphodiesterase inhibitor). Gentamicin (10, 30, 100$\mu$g/m1) did not have an effect on relaxation of phenylephrine-precontracted aortic rings but high concentration of gentamicin(100, 300$\mu$g/ml) relaxed KCl-precontracted aortic rings, which relaxation was potentiated by treatment of nifedipine. Whereas gentamicin markedly decreased left ventricular developed pressure (LVDP) in perfused heart. These data suggest that gentamicin has significant blood pressure lowering of the rat, which seems to be mediated by calcium channel-sensitive pathway and blood $Ca^{2+}$ level may be important role in this response.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.27-37
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• 1990

The extrafetal transfer of $Li^{+}$ in amniotic fluid was studied in 45 pregnant rabbits. LiCl solution was administered either intravenously to mother or directly into the amniotic sac and monitored the appearance and disappearance of $Li^{+}$ in the amniotic fluid, then calculated the transfer rate of $Li^{+}$ of extrafetal origin. To study the transplacental $Li^{+}$ transfer, a solution of 150 mM LiCl was infused continuously via maternal vein (initial dose: 0.7 mmol/kg, maintaining dose: 0.03 mmol/kg/min) and the $Li^{+}$ concentration was measured in maternal blood and amniotic fluid after 60 and 120 minutes of infusion. Change in the volume of aminotic fluid was determined by Congo red dilution method at the same time. Effects of duration of gestation was not considered in this study. Extrafetal transport of $Li^{+}$ into the amniotic fluid was estimated by comparing the $Li^{+}$ concentration and volume of amniotic fluid determined before and after ligating the placental vessels. Extrafetal $Li^{+}$ transport from the amniotic fluid was determined by observing the time dependent disappearance of $Li^{+}$ and Congo red in amniotic fluid after injecting 0.5 ml solution of 15 mM or 90 mM LiCl and 50 mg/ml Congo red. Following are the results obtained: 1) During infusion of LiCl through maternal vein the ratio of the aminotic $Li^{+}$/maternal plasma $Li^{+}$ increased significantly along with the increment of fetal weight. 2) The volume of amniotic fluid of larger fetuses than 20.5 gm increased significantly during administration of LiCl while that of smaller fetuses did not change. 3) After umbilical cord ligation the $Li^{+}$ concentration of amniotic fluid of larger fetuses than 20.5 gm was decreased to $59.9{\pm}10.3%$ and $56.9{\pm}42.9%$ $(mean{\pm}S.D.)$ of those of control group after 60 and 120 minutes of LiCl infusion respectively. In amniotic fluid of smaller fetuses than 20.5 gm, there was no significant difference between control and ligation groups. 4) The disappearance rate of Congo red in the amniotic fluid was $45.2{\pm}8.2%/hr$. 5) The disappearance rate of $Li^{+}$ after intraamniotic injection of LiCl depended on the amount injected. On injecting $7.5\;{\mu}mol$ LiCl, $Li^{+}$ disappeared rapidly from the amniotic fluid and the rates after 60 min and 90 min were $97.0{\pm}2.8,\;98.5{\pm}2.0%$ respectively. On injecting $45\;{\mu}mol$ LiCl, the rates were $56.0{\pm}15.4,\;78.9{\pm}14.5%$ at 60 and 90 min. 6) From the above results it was concluded: a) $Li^{+}$ transfer into the amniotic fluid increased along with the fetal growth and one half of $Li^{+}$ influx is through the extrafetal route even after the maturation of fetal kidney. b) One half of the $Li^{+}$ transfer from the amniotic fluid was through swallowing of fetus, while the remaining half was transfered rapidly through amniotic membrane, which was concentration limited.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.194-194
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• 2017

Camelina (Camelina sativa L.) is a potential bio-energy crop that has short life cycle about 90 days and contains high amount of unsaturated fatty acid which is adequate to bio-diesel production. Enhancing environmental stress tolerance is a main issue to increase not only crop productivity but also big mass production. CsRCI2s (Rare Cold Inducible 2) are cold and salt stress related protein that localized at plasma membrane (PM) and assume to be membrane potential regulation factor. These proteins can be divide into C-terminal tail (CsRCI2D/E/F/G) or no-tail group (CsRCI2A/B/C/H). However, function of CsRCI2s are less understood. In this study, physiological responses and functional characterization of CsRCI2s of Camelina under salt stress were analyzed. Full-length CsRCI2s (A/B/E/F) and CsPIP2;1 sequences were confirmed from Camelina genome browser. Physiological investigations were carried out using one- or four-week-old Camelina under NaCl stress with dose and time dependent manner. Transcriptional changes of CsRCI2A/B/E/F and CsPIP2;1 were determined using qRT-PCR in one-week-old Camelina seedlings treated with NaCl. Translational changes of CsRCI2E and CsPIP2;1 were confirmed with western-blot using the antibodies. Water transport activity and membrane potential measurement were observed by cRNA injected Xenopus laevis oocyte. As results, root growth rate and physiological parameters such as stomatal conductance, chlorophyll fluorescence, and electrolyte leakage showed significant inhibition in 100 and 150 mM NaCl. Transcriptional level of CsPIP2;1 did not changed but CsRCI2s were significantly increased by NaCl concentration, however, no-tail type CsRCI2A and CsRCI2B increased earlier than tail type CsRCI2E and CsRCI2F. Translational changes of CsPIP2;1 was constitutively maintained under NaCl stress. But, accumulation of CsRCI2E significantly increased by NaCl stress. CsPIP2;1 and CsRCI2A/B/E/F co-expressed Xenopus laevis oocyte showed decreased water transport activity as 61.84, 60.30, 62.91 and 76.51 % at CsRCI2A, CsRCI2B, CsRCI2E and CsRCI2F co-expression when compare with single expression of CsPIP2;1, respectively. Moreover, oocyte membrane potential was significantly hyperpolarized by co-expression of CsRCI2s. However, higher hyperpolarized level was observed in tail-type CsRCI2E and CsRCI2F than others, especially, CsRCI2E showed highest level. It means transport of $Na^+$ ion into cell is negatively regulated by expression of CsRCI2s, and, function of C-terminal tail is might be related with $Na^+$ ion influx. In conclusion, accumulation of NaCl-induced CsRCI2 proteins are related with $Na^+$ ion exclusion and prevent water loss by CsPIP2;1 under NaCl stress.

• Natural Product Sciences
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• v.19 no.1
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• pp.36-48
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• 2013

The aim of the present study was to investigate the effects of several fractions obtained from methylene chloride ($CH_2Cl_2$) extract of self-fermented pine needle (SFPNE) on the acetylcholine (ACh)-evoked CA release from the isolated perfused model of the rat adrenal medulla and to establish the mechanism of the most active fraction (Fr.)-induced inhibitory action on the CA release. We obtained 6 fractions from $CH_2Cl_2$ extract of self-fermented pine needle. For the ACh (5.32 mM)-evoked CA release, the following rank order of inhibitory potency was obtained: Fr.4-5 > Fr.8-11 ${\gg}$ Fr.3 > Fr.6 = Fr.7 > Fr.1-2. Fr. 4 - 5 (60 ${\mu}g/mL$) perfused into an adrenal vein for 90 min produced relatively time-dependent inhibition of the CA secretory responses to ACh (5.32 mM), DMPP (100 ${\mu}M$), McN-A-343 (100 ${\mu}M$) and high $K^+$ (56 mM). Fr. 4 - 5 itself did not affect basal CA secretion. Also, in the presence of Fr. 4 - 5 (60 ${\mu}g/mL$), the CA secretory responses to angiotensin II (AngII, 0.1 ${\mu}M$), veratridine (50 ${\mu}M$), Bay-K-8644 (10 ${\mu}M$), and cyclopiazonic acid (10 ${\mu}M$) were significantly reduced, respectively. In the simultaneous presence of Fr. 4 - 5 (60 ${\mu}g/mL$) and L-NAME (30 ${\mu}M$), the inhibitory responses of Fr. 4 - 5 on the CA secretion evoked by ACh, DMPP, high $K^+$, AngII, Bay-K-8644 and veratridine were considerably recovered to the extent of the corresponding control secretion compared with that of Fr. 4 - 5-treatment alone. The level of NO released from adrenal medulla after the treatment of Fr. 4 - 5 (60 ${\mu}g/mL$) was greatly elevated compared with the basal level. Taken together, these results demonstrate that Fr. 4 - 5 inhibits the CA secretion from the isolated perfused rat adrenal medulla evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of Fr. 4 - 5 is mediated by blocking the influx of $Ca^{2+}$ and $Na^+$ into the adrenomedullary chromaffin cells as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store, which is evoked at least partly through the increased NO production due to the activation of NO synthase. Based on these results, it is also thought that Fr. 4 - 5 isolated from $CH_2Cl_2$ extract of pine needle may contain beneficial antihypertensive components to prevent or treat hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.591-598
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• 2017

Propofol is known to cause vasorelaxation of several systemic vascular beds. However, its effect on the pulmonary vasculature remains controversial. In the present study, we investigated the effects of propofol on human pulmonary arteries obtained from patients who had undergone surgery. Arterial rings were mounted in a Multi-Myograph system for measurement of isometric forces. U46619 was used to induce sustained contraction of the intrapulmonary arteries, and propofol was then applied (in increments from $10-300{\mu}m$). Arteries denuded of endothelium, preincubated or not with indomethacin, were used to investigate the effects of propofol on isolated arteries. Propofol exhibited a bifunctional effect on isolated human pulmonary arteries contracted by U46619, evoking constriction at low concentrations ($10-100{\mu}m$) followed by secondary relaxation (at $100-300{\mu}m$). The extent of constriction induced by propofol was higher in an endothelium-denuded group than in an endothelium-intact group. Preincubation with indomethacin abolished constriction and potentiated relaxation. The maximal relaxation was greater in the endothelium-intact than the endothelium-denuded group. Propofol also suppressed $CaCl_2$-induced constriction in the 60 mM $K^+$-containing $Ca^{2+}$-free solution in a dose-dependent manner. Fluorescent imaging of $Ca^{2+}$ using fluo-4 showed that a 10 min incubation with propofol ($10-300{\mu}m$) inhibited the $Ca^{2+}$ influx into human pulmonary arterial smooth muscle cells induced by a 60 mM $K^+$-containing $Ca^{2+}$-free solution. In conclusion, propofol-induced arterial constriction appears to involve prostaglandin production by cyclooxygenase in pulmonary artery smooth muscle cells and the relaxation depends in part on endothelial function, principally on the inhibition of calcium influx through L-type voltage-operated calcium channels.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.118-125
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• 2008

Gardenia jasminoides (G. jasminoides) is traditionally used to treat insomnia, jaundice, emotional disorders, hepatic disease, and inflammatory disease. Previously, we found that geniposide and the water extract of G. jasminoides increased $Cl^-$ influx in neuroblastoma. Here we examined the sychopharmacological activities of G. jasminoides and its constituents. G. jasminoides extract was orally administered at 100 and 200 mg/kg, and genipin and geniposide were intraperitoneally injected at 2, 10, and 20 mg/kg. G. jasminoides extract (200 mg/kg) significantly decreased total open field activity but increased rearing activity in the center of the open field, suggesting an increase in exploratory activity. Genipin and geniposide did not change open field activity, but geniposide (20 mg/kg) increased rearing activity in the central area. The extract (200 mg/kg) significantly decreased rotarod and wire-balancing activity, but genipin and geniposide did not. No compounds influenced thiopental-induced sleeping or electroshock-induced seizures. The extract (200 mg/kg) significantly increased staying time in the open arms of the elevated plus maze and the entry ratio into the open arms, and geniposide (20 mg/kg) also increased open arm entry. Electroshock stress decreased open arm activity, but the extract and geniposide (20 mg/kg) significantly reversed that effect. This results indicate that G. jasminoides extract and geniposide alleviated anxiety with greater efficacy in stressed animals than normal animals.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.69-75
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• 2005

TRPM7, a cation channel protein permeable to various metal ions such as $Mg^{2+}$, is ubiquitously expressed in variety of cells including lymphocytes. The activity of TRPM7 is tightly regulated by intracellular $Mg^{2+}$, thus named $Mg^{2+}$-inhibited cation (MIC) current, and its expression is known to be critical for the viability and proliferation of B lymphocytes. In this study, the level of MIC current was compared between immature (WEHI-231) and mature (Bal-17) B lymphocytes. In both cell types, an intracellular dialysis with $Mg^{2+}$-free solution (140 mM CsCl) induced an outwardly-rectifying MIC current. The peak amplitude of MIC current and the permeability to divalent cation ($Mn^{2+}$) were several fold higher in Bal-17 than WEHI-231. Also, the level of mRNAs for TRPM7, a molecular correspondence of the MIC channel, was significantly higher in Bal-17 cells. The amplitude of MIC was further increased, and the relation between current and voltage became linear under divalent cation-free conditions, demonstrating typical properties of the TRPM7. The stimulation of B cell receptors (BCR) by ligation with antibodies did not change the amplitude of MIC current. Also, increase of extracellular $[Mg^{2+}]_c$ to enhance the $Mg^{2+}$ influx did not affect the BCR ligation-induced death of WEHI-231 cells. Although the level of TRPM7 was not directly related with the cell death of immature B cells, the remarkable difference of TRPM7 might indicate a fundamental change in the permeability to divalent cations during the development of B cells.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.27-36
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• 2017

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of $GABA_A$-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and $0.1{\mu}g/ml$) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of $GABA_A$-ergic systems, and can be useful in the treatment of insomnia.

• YAKHAK HOEJI
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• v.32 no.6
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• pp.402-414
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• 1988

In order to clarify the receptor types and mechanisms underlying the positive inotropic effect of dopamine on the mammalian ventricular myocardium, the action potential, its first derivatives and isometric contraction of the rabbit papillary muscle were recorded using a force transducer and glass capillary microelectrodes filled with 3M KCl. The results were as follows; (1) In normal Tyrode solution, the contractile force was increased and duration of action potential was shortened with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (2) The dose-response curve was markedly shifted to the right by pretreatment with reserpine (5mg/kg i.p., 24hrs prior to the experiment). (3) In 19mM $K^+-Tyrode$ solution, the duration of action potential, maximum rate of rise (V_{max}) of action potential and overshoot were significantly increased with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (4) The inotropic effect of dopamine on the rabbit papillary muscle pretreated with reserpine was antagonized by atenolol ($10^{-6}M$), but not by phentolamine ($3{\times}10^{-6}M$). (5) In rabbit papillary muscle partially depolarized by 19mM $K^+-Tyrode$ solution, slow electrical response (calcium mediated action potential) as well as contraction were restored by dopamine ($10^{-4}M$); this restoration was blocked by calcium antagonists ($3{\times}10^{-5}M$ $LaCl_3{\cdot}6H_2O$, $3{\times}10^{-6}M$ diltiazem) or ${\beta}-adrenoceptor$ antagonist ($3{\times}10^{-6}M$ atenolol), but not affected by ${\alpha}-adrenoceptor$ antagonist ($10^{-5}M$ phentolamine, $3{\times}10^{-6}M$ yohimbine) or vascular dopaminergic receptor antagonist ($10^{-5}M$ haloperidol). The above results may be interpreted as that the positive inotropic effect of dopamine through both direct and indirect action are caused by increase in slow inward current ($Ca^{2+}$ influx into themyocardial cell), and the direct action is mainly due to the stimulation of ${\beta}-adrenoceptors$ in the rabbit papillary muscle.

• Preventive Nutrition and Food Science
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• v.15 no.3
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• pp.189-195
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• 2010

Water extracts from 20 medicinal plants, traditionally used for postmenopausal symptoms in Korea, were examined for their vasorelaxant activity in isolated rat thoracic aorta rings precontracted with norepinephrine (NE). Among the 20 medicinal plants, Cornus officinalis (CoEx, 0.3 mg/mL), Schisandra chinensis (ScEx, 0.3 mg/mL), Erythrina variegate (EvEx, 0.3 mg/mL), and Epimedium koreanum (EkEx, 0.3 mg/mL) showed rapid relaxation of endothelium-intact aorta ($69\pm4%$, $40\pm3%$, $25\pm2%$, and $23\pm3%$ of active tone induced by NE, respectively). In contrast, the extracts of Erythrina variegata (EvEx), Angelica gigas (AgEx), Pueraria thunbergiana (PtEx), and EkEx lead to gradual (i.e., long-term) relaxation to baseline in endothelium-intact vessels. The time to complete relaxation was 20～40 min. These 6 plant extracts were selected for the investigation of possible underlying mechanisms. The CoEx-, ScEx-, or EkEx-induced rapid relaxations were virtually abolished by endothelium denudation, and were significantly inhibited by pretreatment with nitric oxide (NO) synthase inhibitor $N^G$-nitro-L-arginine (L-NNA, 10 ${\mu}M$), indicating that increased formation of NO might contribute to the endothelium-mediated relaxation. In long-term responses, the endothelium denudation did not affect PtEx-induced relaxation, whereas it delayed responses by EvEx and AgEx, and significantly inhibited the effect of EkEx. Among EvEx, AgEx, and PtEx, EvEx attenuated the $CaCl_2$-induced vasoconstriction in high-potassium depolarized medium, implying that EvEx is involved in inhibition of the extracellular calcium influx to smooth muscle through voltage dependent calcium channels. These results provide the scientific rationale for the interrelationships between the use of 20 medicinal plants and their effects on cardiovascular health in estrogen deficient conditions.