• Biomolecules & Therapeutics
• /
• v.31 no.2
• /
• pp.168-175
• /
• 2023

Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Na_v1.7 or the cardiac sodium channel Na_v1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Na_v1.7 and 0.43 mM for Na_v1.5 at a holding potential of -100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Na_v1.7 and Na_v1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Na_v1.7 and Na_v1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Na_v1.7 or show cardiotoxicity by blocking Na_v1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

• Food Science and Biotechnology
• /
• v.16 no.4
• /
• pp.557-564
• /
• 2007

We prepared caviar analogs encapsulated by calcium-alginate gel membranes as a means to replace higher priced natural caviars. Processing the caviar analogs (beluga type) was optimized by response surface methodology with central composite design. Concentrations of sodium alginate ($X_1$) and $CaCl_2\;(X_2)$ were chosen as the independent variables. In order to compare characteristics of the caviar analogs with the natural caviar, sphericity ($Y_1$), diameter ($Y_2$), membrane thickness ($Y_3$), rupture strength ($Y_4$), rupturing deformation ($Y_5$), and sensory score ($Y_6$) were used as the dependent variables. The sphericity of the caviar analogs showed a similar value to that of natural caviar (over 94%) in the range of independent variables. Generally, the $CaCl_2$ concentration ($X_2$) affected all dependent variables to a greater extent than the sodium alginate concentration ($X_l$), For the multiple response optimization of the 5 dependent variables ($Y_1,\;Y_2,\;Y_4,\;Y_5$, and $Y_6$), the desirability function was defined as the following conditions: target values ($Y_1\;=\;100%,\;Y_2\;=\;3.0\;mm,\;Y_4\;=\;1,470\;g,\;Y_5\;=\;1.1\;mm,\;and\;Y_6\;=\;10\;points$). Membrane thickness ($Y_3$) was eliminated from the dependent variables for multiple response optimization because it could not be measured with an image analyzer. The values of the independent variables as evaluated by multiple response optimization were $X_1\;=\;-0.093$ (78%) and $X_2\;=\;-0.322$ (1.07%), respectively.

• Journal of environmental and Sanitary engineering
• /
• v.16 no.4
• /
• pp.1-8
• /
• 2001

We have previously demonstrated that sodium molybdate(Mo) improved lead-intoxicated status by enhancing the metabolism of mao-inositol-related phospholipids in sciatic nerves isolated from rats. In this study, in order to address the reduction mechanism of Mo for lead toxicity, effects of Mo on cystidine-diglyceride transferase, phosphatidylinositol kinase, and phosphatidyl inositol-4-phosphate kinase, involved in mao-inositol metabolism of nerve, were investigated in vivo and in vitro. Mo significantly increased the activities of cystidine- diglyceride transferase and phosphatidylinositol kinase in lead-intoxicated rat, and the pattern of increase was dose-dependent manner. However, Mo did not affect the activity of phosp- hatidylinositiol-4-phosphate kinase in normal and lead-intoxicated rats. We also found that Mo affected the activities of phopholipid metabolism-related enzymes not by the indirect manner such as activation of another metabolic pathway but by the direct manner. These results suggest that the improvement mechanism of Mo for lead-intoxicated status might be a normalization of the activities of phospholipid metabolism-related enzymes in sciatic nerve.

• Journal of the Korean Applied Science and Technology
• /
• v.6 no.2
• /
• pp.29-37
• /
• 1989

Using the quarternary ammonium salts as phase transfer catalyst, the nucleophilic substitution reaction of 1-chlorooctane with sodium-cyanide was investigate kinetically with respect to the formation of octanenitrile. The product was analyzed with gas chromatograph, and quantity of octanenitrile was measured. The reaction condition was considered by the effect of the reaction temperature, of the species and the amount of catalyst, of the speed of strirring, and of the concentration of reactants. The reaction was carried out in the first order on the concentration of 1-chlorooctane and sodium cyanide, respectively. The over-all order was 2nd. The activation energies for the nucleophilic substitution reaction of 1-chlorooctane and 1-bromooctane under tetrabutylammonium hydrogen-sulfate were calculated as 2.05 and 10.08kcal/mol, respectively. The effect of various caltalysts was decreased in the order of tetrabutylammonium bromide, terabutylammonium, tetrabutylammonium hydrogensulfate, and tetrabutylammonium iodide. The reaction rate was dependent on the concentration of sodium-cyanide dissolved in the aqueous phase, and the good result was shown when the mol ratio between 1-chlorooctane and sodium cyanide was one per three.

• Journal of the Korean Chemical Society
• /
• v.31 no.6
• /
• pp.582-589
• /
• 1987

The thermal properties of poly (ethylene terephthalate) (PET) modified by 5-sulfoisophthalic acid sodium salt(SIAS) were studied. The glass transition temperature was increased, and the melting temperature and the crystallization rate were decreased as the content of SIAS unit was increased. The decrease of crystallization rate is thought to be due to the polar, bulky sulfonic acid sodium salt group which greatly retards the crystallization on to the growing crystal surface of the diffused polymer chain. The crystallization mechanism of copolyester is dependent on the content of SIAS unit and the three dimensional growth of crystal is hindered by the added SIAS unit.

• International Journal of Heart Failure
• /
• v.6 no.4
• /
• pp.176-178
• /
• 2024

• The Korean Journal of Physiology
• /
• v.22 no.1
• /
• pp.13-29
• /
• 1988

In order to elucidate the regulatory mechanism of intracellular calcium ion concentrations, contractions or contractures induced by $Na^{+}-removal$, calcium-application or ouabain-treatment as an index of $Na^+/Ca^{2+}$ exchange activity were studied in atrial muscle or vascular smooth muscle (aorta and renal artery) of the rabbit. The magnitude of low sodium contractures in atrial trabeculae increased with sigmoid shape when external sodium concentrations were reduced to sodium-free condition, whereas that of calcium contracture intensified in a parabolic pattern when external calcium concentrations were elevated to 8 mM. $Na^{+}-removal$ contractures were induced in a duration-dependent manner to $K^{+}-free$ exposure and same findings were observed with ouabain treatment. $Na^{+}-free$ contractures were not affected by verapamil treatment, but stimulated by $100{\mu}M\;Mn^{2+}$ and inhibited by high concentrations of $Mn^{2+}\;(2{\sim}8mM)$ in a dose-dependent manner. Ryanodine which is known to suppress the release of calcium from internal store abolished spontaneous twitch contractions induced by $K^{+}-free$ solution, but had no effect on the development $Na^{+}-free$ contractures. Na-free contractures were not always induced in vascular smooth muscle preparations. Contractures by $O\;mM\;Na^+$ were usually seen in aorta, but not often in renal artery.$50\;mM\;K^+$, noradrenaline (NA) and angiotensin II (AII) always evoked very large contraction in all preparations of vascular smooth muscle. Contractures developed by $O\;mM\;Na^+$ were not sensitive to verapamil treatment as in atrial trabeculae, but were abolished by $100{\mu}M\;Mn^{2+}$. In contrast to $Na^{+}-free$ contractures, $Mn^{2+}(100{\mu}M)$ had no effect on the contractures induced by NA or 50 mM$K^+$. Caffeine in the concentration of 10 mM evoked transient contracture in the distal renal artery. The rate of spontaneous relaxation in caffeine contracture was dependent upon the concentrations of external sodium, and had double component of relaxation when the rate of relaxation was plotted in the semilogarithmic scale of relative tension versus time. Especially late components of relaxation had more direct relation to $Na^+$ concentrations. It could be concluded that $Na^+/Ca^{2+}$ exchange mechanism in the heart has a large capacity, inhibited by $Mn^{2+}$ but not by verapamil and ryanodine, while $Na^+/Ca^{2+}$ exchange system in vascular smooth muscle has a very low capacity especially in small artery, inhibited by low concentration of $Mn^{2+}\;(100{\mu}M)$ but not affected by verapamil and ryanodine.

• The Korean Journal of Physiology
• /
• v.28 no.2
• /
• pp.181-190
• /
• 1994

Endothelium-derived relaxing factor (EDRF) activates guanylate cyclase which mediates the formation of cGMP from GTP in vascular smooth muscle. It is well known that endothelium-dependent relaxation is impaired in spontaneously hypertensive rats (SHR). However, it is still unknown whether the impaired endothelium-dependent relaxation in SHR results from the reduced release of EDRF or from the decrease of vascular response to EDRF. We investigated the effects of cGMP on the contractility and Ca movement in the aorta of SHR and Wistar-Kyoto rats (WKY). The amplitude of the endothelium-dependent relaxation to actylcholine (ACh) was significantly less in SHR than in WKY. L-arginine $(10^{-3}M)$ did not increase endothelium-dependent relaxation in both strains. Sodium nitroprusside (SNP), an activator of guanylate cyclase, relaxed the 40 mM $K^+-induced$ contraction in a dose-dependent manner $(10^{-10}{\sim}10^{-6}\;M)$ in the endothelium-rubbed aortic strips of both strains. However, there was no significant difference in these relaxations between WKY and SHR. 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP), a cell membrane-permeable derivative of cGMP relaxed the 40 mM $K^+-induced$ contraction in a dose-dependent manner $(10^{-6}{\sim}10^{-4}\;M)$ in the endothelium-rubbed aortic strips of both strains. Also norepinephrine $(10^{-6}\;M)-induced$ contractions in normal and Ca-free Tyrode's solution were suppressed by the pretreatment with 8-Br-cGMP $(10^{-4}\;M)$ in either strain. However, the amplitudes of suppression induced by 8-Br-cGMP were greater in SHR than that in WKY. Basal $^{45}Ca$ uptake and 40mM $K^+-stimulated\;^{45}Ca$ uptake were not suppressed by pretreatment with 8-Br-cGMP $(10^{-4}\;M)$ in single aortic smooth muscle cells of both SHR and WKY. From the above results, it is suggested that cGMP decreases Ca sensitivity in vascular smooth muscle cells and that the impaired endothelium-dependent relaxation in the aortic strips of SHR is not the result of a reduced vascular response to EDRF.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.29 no.4
• /
• pp.305-312
• /
• 2015

Paeonol is a major component found in the Paeoniaceae family such as Paeonia suffruticosa Andrews. Paeonia suffruticosa Andrews has traditionally been used to enhance blood flow and relieve joint pain in east Asian countries including China, Korea and Japan. Current research has shown that paeonol blocked the voltage-gated sodium channel and L-type calcium channel. However, there is a lack of research to reveal the relation between cardiac function and blockade of ion channels by paeonol. Therefore, the aim of this study is to investigate whether paeonol has anti-arrhythmic effects via modulating cardiac ion channels. It is collected that the effects of paeonol on multiple ion channels such as the fast sodium channel and L-type calcium channel from published papers. To incorporate the information on multi-channel block, we computed the effects using the mathematical cardiac model of the guinea-pig and rat ventricular cells (Noble 1998 and 1991 model) and induced early after-depolarizations (EADs) to generate an arrhythmia in the whole heart. Paeonol slightly shortened the action potential duration in the normal cardiac ventricular action potential by the inhibition of sodium channel and L-type calcium channel. Paeonol presented the protective effect from EADs by the inactivation of sodium channel but not L-type calcium channel. Paeonol did not show any changes when it treated on normal ventricular cells through the inhibition of sodium channel, but the protective effect of paeonol through sodium channel on EADs was dose-dependent. These findings suggest that paeonol and its original plant may possess anti-arrhythmic activity, which implies their cardioprotective effects.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.5
• /
• pp.537-546
• /
• 1997

It has been postulated that the intracellular taurine is co-transported with $Na^+$down a concentration gradient and prevents the intracellular accumulation of sodium. It is therefore, expected that an elevated level of intracellular taurine prevents the sodium-promoted calcium influx to protect the cellular damages associated with sodium and calcium overload. In the present study, we evaluated the effects of intra- and extracellular taurine on the myocardial $Na^+$and$Ca^{++}$ contents and the cardiac functions in isolated rat hearts which were loaded with sodium by monensin, a $Na^+-ionophore$. Monensin caused a dose-dependent increase in intracellular $Na^+$ accompanied with a subsequent increase in intracellular $Ca^{++}$ and a mechanical dysfunction. In this monensin-treated heart, myocardial taurine content was decreased with a concomittent increase in the release of taurine. The monensin-induced increases in intracellular $Na^+$, $Ca^{++}$ and depression of cardiac function were prevented in the hearts of which taurine content had been increased by high-taurine diet. Conversely, in the hearts of which taurine concentration gradient had been decreased by addition of taurine in the perfusate, the monensin-induced increases in $Na^+$, $Ca^{++}$ and functional depression were accelerated. These results suggest that taurine, depending on the intra-extracellular concentration gradient, can affect intracellular sodium and calcium concentrations, and that an increased intracellular taurine may play a role in protection of myocardial dysfunction associated with the sodium and calcium overload.