• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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• pp.379-383
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• 2009

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.4
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• pp.341-346
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• 2014

Lubiprostone is a chloride ($Cl^-$) channel activator derived from prostaglandin $E_1$ and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid $EP_1$, $EP_2$, $EP_3$, and $EP_4$ antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [$K^+$] channel blocker) and apamin (a calcium [$Ca^{2+}$]-dependent $K^+$ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive $K^+$ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive $K^+$ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive $K^+$ channel through a prostanoid EP receptor-independent mechanism.

• The Korean Journal of Physiology
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• v.29 no.1
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• pp.61-67
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• 1995

The extract of Ginkgo bibloba (EGb) is a complex mixture of natural products from the Ginkgo leaves and clinically used for the treatment of cerebral and peripheral circulatory disturbances due to its combined activity of several vasoactive principles. In this study we investigated the action of EGb and its mechanism in isolated rabbit corporal smooth muscle to evaluate the possibility of using this material as a pharmacoerecting agent. Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. EGb began to exert an relaxing effect at 1 mg/ml in the submaximally precontracted muscle strips with phenylephrine $(PHE,\;5{\times}10^{-6}\;M)$; causing concentration-dependent relaxation with maximal effect at $3{\sim}5\;mg/ml$. That relaxation was partially inhibited by removal of the smooth muscle endothelium or by pretreatment with a NO scavenger, pyrogallol $(10^{-4}\;M)$ or the guanylate cyclase inhibitor, methylene blue $(10^{-4}\;M)$. Pretreatment with EGb (3 mg/ml) inhibited PHE- $(5{\times}10^{-6}\;M)$ or KCI- (20 and 40 mM) induced contraction of muscle strip. In calcium-free high potassium solution EGb depressed the basal tone of the depolarized muscle strip and inhibited calcium-induced contraction when $CaCl_2$ $(10^{-4}\;M)$ was added. These results suggest that EGb relaxes rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from the corporal sinusoidal endothelium, sequestration of intracytosolic calcium, and maybe a hyperpolarizing action.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.3
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• pp.1-11
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• 2010

Objectives : This study was designed to investigate the effects of Lumbricus extract(LE) on the regional cerebral blood flow(rCBF) in ischemic rats, further to determine the mechanism of action of LE, and the effects that LE inhibits lactate dehydrogenase(LDH) activity in brain cells. Methods and materials : This study, ischemic rats were divided into total four group: control group(n=6), experimental group I (LE treated group)(n=6), experimental group II(LE treated group after pretreatment with indomethacin)(n=6), experimental group III(LE treated group after pretreatment with methylene blue)(n=6). And the measurement that LE inhibits LDH activity in the damage to brain cells to N-methyl-D-aspartic acid(NMDA). The changes of rCBF were determinated by laser-doppler flowmetry(LDF), and LDH activity was determinated by microplate reader in vitro. Results : 1. The rCBF was significantly improved by LE(10 mg/kg, i.p.) during the period of cerebral reperfusion, compared with the control group. 2. The rCBF was significantly increased by LE after pretreatment with indomethacin(1 mg/kg, i.p.), an inhibitor of cyclooxygenase, during the period of cerebral reperfusion, compared with the LE group, and rCBF was accelerated by LE after pretreatment with methylene blue($10{\mu}g/kg$, i.p.) an inhibitor of guanylate cyclase during the period of cerebral reperfusion, compared with the control group. 3. LE significantly inhibited LDH activity in vitro in a dose-dependent manner. Conclusions : From the above results, these were suggested that Lumbricus had anti-ischemia action in connection with cyclooxygenase and might prevent the brain cells death through inhibited LDH activity.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1216-1226
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• 2015

GlxR is considered as a global transcriptional regulator controlling a large number of genes having broad physiological aspects in Corynebacterium glutamicum. However, the expression profile revealing the transcriptional control of glxR has not yet been studied in detail. DNA affinity chromatography experiments revealed the binding of transcriptional regulators SucR, RamB, GlxR, and a GntR-type protein (hereafter denoted as GntR3) to the upstream region of glxR. The binding of different regulators to the glxR promoter was confirmed by EMSA experiments. The expression of glxR was analyzed in detail under various carbon sources in the wild-type and different mutant strains. The sucR and gntR3 deletion mutants showed decreased glxR promoter activities, when compared with the wild type, irrespective of the carbon sources. The promoter activity of glxR was derepressed in the ramB deletion mutant under all the tested carbon sources. These results indicate that SucR and GntR3 are acting as activators of GlxR, while RamB plays a repressor. As expected, the expression of glxR in the cyaB and glxR deletion mutants was derepressed under different media conditions, indicating that GlxR is autoregulated.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.5
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• pp.261-267
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• 2002

The aim of the present study was to investigate the interaction of $estradiol-17{\beta}-bovine$ serum albumin $(E_2-BSA)$ and calcitropic hormones, such as parathyroid hormone, calcitonin, and vitamin D, in regulation of $Ca^{2+}$ uptake in primary cultured renal proximal tubule cells. Statistically significant increase in $Ca^{2+}$ uptake was found from 2 hours after $(E_2-BSA)\;(10^{-9}\;M)$ treatment, while $estradiol-17{\beta}\;(10^{-9}\;M)$ did not affect. Treatment of the cells with $(E_2-BSA)\;(10^{-9}\;M)$ together with parathyroid hormone (PTH) $(10^{-8}\;M),$ vitamin D $(10^{-8}\;M),$ or calcitonin $(10^{-8}\;M)$ significantly stimulated $Ca^{2+}$ uptake by 32.50%, 29.30%, or 27.75%, respectively, compared with the control. However, calcitropic hormones did not exhibit any synergistic effect on the E2-BSA-induced stimulation. $E_2-BSA$ significantly increased cAMP generation and PKC activity. The stimulatory effect of cotreatment of $E_2-BSA$ and PTH or vitamin D was blocked by SQ22536 (an adenylate cyclase inhibitor) and staurosporine (a PKC inhibitor), but the effect of cotreatment of $E_2-BSA$ and calcitonin was not blocked. Furthermore, 8-Br-cAMP and TPA (an artificial PKC promoter) increased $Ca^{2+}$ uptake by 25.51% and 16.47%, respectively, compared with the control. In conclusion, $E_2-BSA$ combined with calcitropic hormones regulated $Ca^{2+}$ uptake partially via cAMP and PKC-dependent mechanisms in renal proximal tubule cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.652-657
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• 2007

This experimental study was designed to investigate the effects of FOENICULI FRUCTUS freeze dry powder (FF) on the change of cerebral hemodynamics [regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP)] in normal and further to determine the mechanism of action of FF. The results in normal rats were as follows ; FF significantly increased rCBF in a dose-dependent, but decreased MABP, This results were suggested that FF significantly increased rCBF by dilating PAD. The FF-induced increase in rCBF was significantly inhibited by pretreatment with 1H[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ, 10 ${\mu}$g/kg, i.p.), an inhibitor of guanylate cyclase and indomethacin (IDN, 1 mg/kg, i.p.), an inhibitor of cyclooxygenase and propranolol (PPN, 3 mg/kg, i.p.), a blocker of adrenalic f receptor and Lu-Nitro-L-Arginine (L-NNA, 1 m9/kB, i.p.), an inhibitor of nitric oxide synthase. The FFE-induced decrease in MABP was significantly increased by pretreatment with L-NNA and was increased by pretreatment with PPN, Dut was inhibited by pretreatment with ODQ and IDN, This results were suggested that the mechanism of FF was mediated by nitric oxide synthase and adrenalic ${\beta}$ receptor.

• Journal of Plant Biotechnology
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• v.41 no.4
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• pp.206-211
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• 2014

Nutritional assessment of transgenic crops to improve safety evaluations is important for food production. An oxidative stress-tolerant rice was generated by stable insertion of the TC gene-a tocopherol cyclase isolated from tobacco-into the genome of a common variety of japonica colored rice. The nutritional composition of the brown rice grains from the transgenic TC line was compared with that of the parental rice cultivar Heugnambyeo and two different varieties of non-transgenic rice. The results indicate that the analyzed nutritional compositions of the brown grains from the transgenic TC line were within the range of values reported for other commercial lines, and measurements of nutritional compositions were equivalent to those of the non-transgenic rice.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.607-612
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• 2001

Endogenous carbon monoxide (CO) shares with nitric oxide (NO) a role as a putative neural messenger in the brain. Both gases are believed to modulate CNS function via an increase in cytoplasmic cGMP concentrations secondary to the activation of soluble guanylate cyclase (sGC). Recently CO and NO were proposed as a possible mediator of febrile response in hypothalamus. NO has been reported to activate both the constitutive and inducible isoform of the cyclooxygenase (COX). Thus, we investigated whether CO arising from heme catabolism by heme oxygenate (HO) is involved in the febrile response via the activation of COX in the hypothalamus. $PGE_2$ which is a final mediator of febrile response released from primary cultured hypothalamic cells was taken as a marker of COX activity. $PGE_2$ concentration was measured with EIA kits. Exogenous CO (CO-saturated medium) and hemin (a substrate and potent inducer of HO) evoked an increase in $PGE_2$ release from hypothalamic cells, and these effects were blocked by methylene blue (an inhibitor of sGC). And membrane permeable cGMP analogue, dibutyryl-cGMP elicited significant increases in $PGE_2$release. These results suggest that there may be a functional link between HO and COX enzymatic activities. The gaseous product of hemin through the HO pathway, CO, might play a role through the modulation of the COX activity in the hypothalamus.

• Mycobiology
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• v.50 no.2
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• pp.121-131
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• 2022

The rare edible and medicinal fungus Antrodia cinnamomea has a substantial potential for development. In this study, Illumina HiSeq 2000 was used to sequence its transcriptome. The results were assembled de novo, and 66,589 unigenes with an N50 of 4413 bp were obtained. Compared with public databases, 6,061, 3,257, and 2,807 unigenes were annotated to the Non-Redundant, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The genes related to terpene biosynthesis in the mycelia of A. cinnamomea were analyzed, and acetyl CoA synthase (ACS2 and ACS4), hydroxymethylglutaryl CoA reductase (HMGR), farnesyl transferase (FTase), and squalene synthase (SQS) were found to be upregulated in XZJ (twig of C. camphora) and NZJ (twig of C. kanehirae). Moreover, ACS5 and 2,3-oxidized squalene cyclase (OCS) were highly expressed in NZJ, while heme IX farnesyl transferase (IX-FIT) and ACS3 were significantly expressed in XZJ. The differential expression of ACS1, ACS2, HMGR, IX-FIT, SQS, and OCS was confirmed by real-time quantitative reverse transcription PCR. This study provides a new concept for the additional exploration of the molecular regulatory mechanism of terpenoid biosynthesis and data for the biotechnology of terpenoid production.