• CELLMED
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• v.4 no.2
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• pp.12.1-12.12
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• 2014

Epinephrine is a critical drug for patients at risk for anaphylaxis. Here, we suggest moxibustion as an alternative method to reduce anaphylaxis. Moxibustion was applied to the Shimen (CV5) acupoint and found to attenuate compound 48/80-induced mortality. Capsazepine, a transient receptor potential vanilloid (TRPV) 1 antagonist, significantly improved overall survival rates compared to groups treated with moxibustion or 2-aminoethoxydiphenyl borate (an activator of TRPV1, 2, and 3). Probenecid (a TRPV2 agonist) also increased survival rate and reduced histamine levels. Survival rates increased by moxibustion and probenecid were completely inhibited by ruthenium red (a TRPV2 and 3 antagonist) and gadolinium chloride (general TRPV antagonist), respectively. Passive cutaneous anaphylaxis and ear swelling were significantly reduced by moxibustion and probenecid (p < 0.05). In cardiomyocytes, TRPV2 was over-expressed by compound 48/80 and histamine but this increased TRPV2 expression decreased to baseline with moxibustion and probenecid treatment. In addition, intracellular calcium levels increased by compound 48/80 were reduced by probenecid. Overall, these findings suggest that the reduction of anaphylaxis caused by moxibustion could represent a new mechanism of moxibustion related to the regulation of TRPV2 activation and promotion of epinephrine secretion.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.197-210
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• 2000

Suppressive role of $Na^+-Ca^{2+}$ exchange in myocardial tension generation was examined in the negative frequency-force relationship (FFR) of electric field stimulated left atria (LA) from postnatal developing rat heart and in the whole-cell clamped adult rat ventricular myocytes with high concentration of intracellular $Ca^{2+}$ buffer (14 mM EGTA). LA twitch amplitudes, which were suppressed by cyclopiazonic acid in a postnatal age-dependent manner, elicited frequency-dependent and postnatal age-dependent enhancements after $Na^+-reduced,\;Ca^{2+}-depleted$ (26 Na-0 Ca) buffer application. These enhancements were blocked by caffeine pretreatment with postnatal age-dependent intensities. In the isolated rat ventricular myocytes, stimulation with the voltage protocol roughly mimicked action potential generated a large inward current which was partially blocked by nifedipine or $Na^+$ current inhibition. 0 Ca application suppressed the inward current by $39{\pm}4%$ while the current was further suppressed after 0 Na-0 Ca application by $53{\pm}3%.$ Caffeine increased this inward current by $44{\pm}3%$ in spite of 14 mM EGTA. Finally, the $Na^+$ current-dependent fraction of the inward current was increased in a stimulation frequency-dependent manner. From these results, it is concluded that the $Ca^{2+}$ exit-mode (forward-mode) $Na^+-Ca^{2+}$ exchange suppresses the LA tension by extruding $Ca^{2+}$ out of the cell right after its release from sarcoplasmic reticulum (SR) in a frequency-dependent manner during contraction, resulting in the negative frequency-force relationship in the rat LA.

• Preventive Nutrition and Food Science
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• v.6 no.1
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• pp.43-50
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• 2001

The effects of cardiac ischemia-reperfusion and $\beta$-adrenergic stimulation on metabolic function and energetics were investigated in Lan gendorff-perfused spontaneously hypertensive rat (SHR) hearts. Sarcoplasmic reticulum {TEX}$Ca^{2+}${/TEX}-dependent ATPase and cardiac lactate dehydrogenase (LDH) are additionally studied. The perfusion medium (1.0 mM {TEX}$Ca^{2+}${/TEX}) contained 5 mM glucose(+5 U/L insulin) and 2 mM pyruvate as substrates. Global ischemia was induced by reducing perfusion pressure of 100 to 40 cm {TEX}$H_{2}${/TEX}O, followed by 20 min reperfusin. Isoproterenol (ISO, 1$\mu$M) was infused for 10 min. Coronary vascular resistance and myocardial oxygen consumption ({TEX}$MVO_{2}${/TEX}) of SHR were increased in parallel with enhanced venous lactate during ischemia and reperfusion compared to those of Sprague Dawley (SD) hearts. Although ischemia-induced increase in venous lactate and combined adenosine plus inosine was abolished, coronary vasodilation produced in SD during reperfusion. In SHR, depressed reactive hyperemia was associated with a fall in cardiac ATP and CrP/Pi ratio and a rise in intracellular lactate/Pyruvate ratio. On the other hand, ISO produced coronary functional hyperemia and an increase in {TEX}$MVO_{2}${/TEX}. However, these responses were less than those in SHR hearts. The ATPase activity of SHR was attenuated in free {TEX}$Ca^{2+}${/TEX} concentrations used under basal condition and with ISO compared to that of SD. Venous lactate output and cardiac LDH activity were augmented in SHR as influenced by ISO. These results demonstrate that coronary reactive and functional hyperemia was dpressed in SHR, which cold be explained by alterations in the cytosolic phosphorylation potential and the cytosolic redox state manipulated by LDH, and by abnormal free calcium handling.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.1
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• pp.15-21
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• 2017

Objective: The aims of this study were to investigate whether fertilization could induce the resumption of meiosis in mouse oocytes arrested at metaphase I (MI) after in vitro maturation (IVM), and to investigate the effect of $Ca^{2+}$ chelator treatment at the time of fertilization on the transition from MI to metaphase II (MII). Methods: MII-stage and arrested MI-stage mouse oocytes after IVM were fertilized, and then embryonic development was monitored. Blastocysts from each group were transferred into 2.5 days post-coitum pseudo-pregnant ICR mice. MI oocytes after IVM were treated with a $Ca^{2+}$ chelator to investigate the effect of $Ca^{2+}$ oscillations on their maturation. Results: As insemination time increased, the number of oocytes in the MI group that reached the MII stage also increased. The blastocyst rates and total cell numbers in the MII group were significantly higher than in the MI group. No pregnancy occurred in the MI group, but 10 pregnancies were achieved (10 of 12) in the MII group. The proportion of MI oocytes that matured to MII oocytes after fertilization was significantly higher in the non-treated group than in the $Ca^{2+}$ chelator-treated group. Conclusion: The findings that a higher proportion of MI-arrested oocytes progressed to MII after fertilization and that the MI-to-MII transition was blocked by $Ca^{2+}$ chelator treatments before fertilization indicate that the maturation of MI oocytes to MII oocytes is associated with intracellular $Ca^{2+}$ oscillations driven by fertilization.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.9-21
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• 2015

Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancer-related mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.

• International Journal of Oral Biology
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• v.39 no.4
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• pp.229-236
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• 2014

Reactive oxygen species (ROS) and nitrogen species (RNS) are implicated in cellular signaling processes and as a cause of oxidative stress. Recent studies indicate that ROS and RNS are important signaling molecules involved in nociceptive transmission. Xanthine oxidase (XO) system is a well-known system for superoxide anions ($O{_2}^{{\cdot}_-}$) generation, and sodium nitroprusside (SNP) is a representative nitric oxide (NO) donor. Patch clamp recording in spinal slices was used to investigate the role of $O{_2}^{{\cdot}_-}$ and NO on substantia gelatinosa (SG) neuronal excitability. Application of xanthine and xanthine oxidase (X/XO) compound induced membrane depolarization. Low concentration SNP ($10{\mu}M$) induced depolarization of the membrane, whereas high concentration SNP (1 mM) evoked membrane hyperpolarization. These responses were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger). Addition of thapsigargin to an external calcium free solution for blocking synaptic transmission, led to significantly decreased X/XO-induced responses. Additionally, X/XO and SNP-induced responses were unchanged in the presence of intracellular applied PBN, indicative of the involvement of presynaptic action. Inclusion of GDP-${\beta}$-S or suramin (G protein inhibitors) in the patch pipette decreased SNP-induced responses, whereas it failed to decrease X/XO-induced responses. Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) decreased the effects of SNP, suggesting that these responses were mediated by direct oxidation of channel protein, whereas X/XO-induced responses were unchanged. These data suggested that ROS and RNS play distinct roles in the regulation of the membrane excitability of SG neurons related to the pain transmission.

• Korean Journal of Medicinal Crop Science
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• v.19 no.1
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• pp.31-37
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• 2011

Previous work demonstrated that an ethanol extract (HS0608) of a mixture of three medicinal plants of Curcuma longae radix, Phellinus linteus, and Scutellariae radix markedly inhibits $A{\beta}$ (25-35)-induced neurotoxicity. The present study was performed to further verify the neuroprotective effect of HS0608 on oxidative and ischemic cerebral injury using cultured rat cortical neurons and rats. Exposure of cultured cortical neurons to $100\;{\mu}M$ hydrogen peroxide ($H_2O_2$) induced neuronal apoptotic death. At $10-100{\mu}g/ml$, HS0608 inhibited neuronal death, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) induced by $H_2O_2$ in primary cultures of rat cortical neurons. In vivo, HS0608 prevented cerebral ischemic injury induced by 2-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct and edema were significantly reduced in rats that received HS0608 (200 mg/kg). These results suggest that the anti-oxidative properties of HS0608 may be responsible for its neuroprotective effect against focal cerebral ischemic injury and that HS0608 may have a therapeutic role in neurodegenerative diseases such as stroke.

• The Korean Journal of Physiology
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• v.26 no.1
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• pp.45-54
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• 1992

Effects of pH, $PCO_2$, and adenosine on the vascular contractility were investigated in the pig coronary arteries. The helical strips of isolated coronary arteries were immersed in the HEPES or $HCO_3^-/CO_2$-buffered Tyrode's solution equilibrated with 100% $O_2\;or\;95%\;O_2-5%\;CO_2\;at\;35^{\circ}C$. The contraction was recorded isometrically using a force transducer. The amplitudes of contraction induced by ACh, high $K^+$, and electrical Held stimulation (EFS) were decreased by elevating extracellular pH (pHo) and were increased by lowering pHo. A shift from $0%\;CO_2\;to\;5%\;CO_2$ at constant pHo (pH 7.4) reduced the contractions induced by ACh, high $K^+$, EFS. However the contraction induced by 100mM $K^+$ was less influenced by the change of pHo or $CO_2$. The contraction induced by ACh in $Ca^{2+}$free Tyrode's solution as well as the contraction developed by the addition of extracellular of $Ca^{2+}$ were decreased by lowering pHo and were increased by elevating pHo. High $K^+$ (25mM) induced contraction at pH 6.8 was not returned to the level of the contraction at pH 7.4 by the elevation of extracellular. calcium $[Ca^{2+}]_o$. Adenosine-induced relaxation was more significant with 5% $CO_2$ than 0% $CO_2$ in the high $K^+$-induced contraction and was more significant with low pHo than high pHo in the contraction induced by EFS. From the above results, it is suggested that $H^+$ and $CO_2$ inhibit $Ca^{2+}$ influx as well as $Ca^{2+}$ release from intracellular $Ca^{2+}$ storage sites and enhance the relaxing effect of adenosine in the pig coronary artery.

• The Korean Journal of Physiology
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• v.25 no.1
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• pp.61-67
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• 1991

In order to determine possible relationships between the renin-angiotensin system and nephron heterogeneity, we compared the response of renin release and the angiotensin-converting enzyme (ACE) activity from different areas of the rat kidney. We used the renal cortical slices from the capsular surface to the juxtamedullary junction. Slices from outer one-third of the cortex were designated as outer cortical slices (OC), middle one-third as midcortical slices (MC), and inner one-third as inner cortical slices (IC). The renal renin content markedly decreased from OC and MC to IC. The basal lenin release was higher in OC than in MC or IC. On the contrary the percent change of renin release in response to L-isoproterenol was significantly higher in MC than in OC or IC. By TMB-8, the renin release in MC by $231{\pm}21%$ was higher than OC by $171{\pm}19%$ or IC by $$162{\pm}19. Angiotensin II suppressed renin release in OC and MC by $68{\pm}2,\;71{\pm}4%$ respectively, but only $40{\pm}7%$ in IC. The ACE activity was higher in IC than in OC, MC, medulla and papilla. The present data indicate that renin content and basal lenin release gradulally decreased from outer (OC) to inner (IC) cortex. The renin release in response to beta-adrenergic agonist, L-isoproterenol and intracellular calcium antagonist, TMB-8 were higher in MC than in OC and IC, but angiotensin II suppressed renin release less in IC than in OC and MC. It is suggested that juxtaglomerular cells of outer, mid-and inner cortices show a difference in renin release response to the stimuli.

• The Korean Journal of Physiology
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• v.25 no.1
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• pp.17-26
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• 1991

Single smooth muscle cells of the rabbit pulmonary artery were isolated by treatment with collagenase and elastase. Using the patch clamp technique, potassium channel activity was recorded from the inside-out membrane patch. The channel had a sin히e channel conductance of about 360 pS in symmetrical concentration of K on both sides of the patch, 150 mM, and had a linear current-voltage relationship. During the application of 10 mM tetraethylammonium (TEA) to the intracellular membrane surface, the amplitude of single channel current was reduced and very rapid flickering appeared. The open probability $(P_0)$ of this channel was increased by increasing positivity of the potential across the patch membrane, with e-fold increase by 20 mV depolarization, and by increasing the internal $Ca^{2+}$ concentration. These findings are consistent with those of large conductance Ca-activated K channels reported in other tissues. But the shortening of the mean open time by increasing $[Ca^{2+}]_i$, was an unexpected result and one additional closed state which might be arisen from a block of the open channel by Ca binding was suggested. The $P_0-membrane$ potential relationship was modulated by internal pH. Decreasing pH reduced $P_0$. Increasing pH not only increased $P_0$ but also weakened the voltage dependency of the channel opening. The modulation of Ca-activated K channel by pH was thought to be related to the mechanism of regulation of vascular tone by the pH change.