• 제목/요약/키워드: $Ca^{2+}$ channel blocker

검색결과 150건 처리시간 0.035초

무 (Raphanus sativus L.) 자엽에서 산화질소 (Nitric oxide)에 의해 유도된 부정근 형성과정에 대한 칼슘의 효과 (Effects of Calcium on Nitric oxide (NO)-induced Adventitious Rooting Process in Radish (Raphanus sativus L.) Cotyledons)

  • 진창덕
    • Journal of Plant Biotechnology
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    • 제34권3호
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    • pp.213-221
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    • 2007
  • 분리된 무 자엽 조직에 산화질소 (nitric oxide: NO) 공여체인 sodium nitroprusside (SNP) 처리 시 농도 의존방식으로 부정근의 발달을 증진시켰다. 그러나 이러한 NO 증진 효과는 세포외 칼슘 chelator인 0.5 mM EGTA 또는 세포막 칼슘채널 차단제인 0.1 mM $LaCl_3$를 각각 $50\;{\mu}M$ SNP와 함께 혼합처리 시 반전되었다. 또한, 뿌리 발생에서 중심적 역할을 수행하는 것으로 알려진 guaiacol peroxidase (GPX)와 syringaldazine peroxidase (SPX)의 활성도가 SNP 단독 처리된 자엽에서 부정근이 형성되는 동안 현저히 증가하였다. 그러나, SNP와 $LaCl_3$ 혼합처리 시 SNP에 의해 유도된 GPX와 SPX 활성도 증가가 거의 증류수 대조구 수준으로 억제되었다. calmodulin의 anatagonist인 trifuoperazine 역시 SNP로 처리된 자엽에서 부정근 형성을 억제하여 발생된 뿌리의 개수와 길이를 감소시켰으며 동시에 GPX와 SPX를 불활성화 하였다. 결론적으로, 이들 결과는 칼슘이 GPX와 SPX 활성도 조절을 통해 부정근 유도를 이끄는 NO 반응에 포함되어 있음을 나타내는 것이다.

Isolation and electrical characterization of the rat spinal dorsal horn neurons

  • Han, Seong-Kyu;Lee, Mun-Han;Ryu, Pan-Dong
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.175-175
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    • 1996
  • The spinal dorsal horn is the area where primary afferent fibers terminate and cutaneous sensory information is Processed. A number of putative neurotransmitter substances, including excitatory and inhibitory amino acids and peptides, are present in this region and sites and cellular mechanisms of their actions have been a target of numerous studies. In this study, single neurons were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by the patch clamp method. Young rats (7-14 days) were anesthetized with diethyl-ether, and the lumbar spinal cord was excised and cut transversely at a thickness of 30$\mu\textrm{m}$ by Vibroslicer. The treatment of spinal slices with low concentration of proteases (pronase and thermolysin 0.75 mg/$m\ell$) and mechanical dissociation yielded isolated neurons with near intact morphology. Multipolar, ellipsoidal and bipolar, and pyramidal cells were shown. By applying step voltage pulses to neurons held at -70 mV, two types of inward currents and one outward currents observed. The fast activating and inactivating inward current was the Na$\^$+/ current because of its fast kinetics and blocking by 0.5${\mu}$M TTX, a specific blocker of Na$\^$+/ channel. The second type of inward currents were sustained. Based on their kinetics and current-voltage relations, it was likely that the second type of inward current was the voltage-dependent Ca$\^$2+/ current. In the presence of TTX, the steady-state currents mainly represented outward K$\^$+/ current which looked like the delayed rectifier K$\^$+/ current. In addition, the membrane currents produced by agonist of excitatory amino acid (EAA) receptor and the endogenous transmitter candidate L-glutamate were recorded in isolated whole-cell voltage clamped neurons as well as responses to inhibitory amino acids (${\gamma}$-amino butyric acid, glycine). Drugs were applied by a method that allows complete exchange of the solution within 1 sec; an infinite number of solutions can be applied to a single cell.

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The Inhibitory Mechanism on Acetylcholine-Induced Contraction of Bladder Smooth Muscle in the Streptozotocin-Induced Diabetic Rat

  • Han, Jong Soo;Kim, Su Jin;Nam, Yoonjin;Lee, Hak Yeong;Kim, Geon Min;Kim, Dong Min;Sohn, Uy Dong
    • Biomolecules & Therapeutics
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    • 제27권1호
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    • pp.101-106
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    • 2019
  • Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, $10^{-4}M$). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine $A_1$ receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an ${\alpha}_1$-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular $Ca^{2+}$ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.

cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

  • Peng, Li-qun;Li, Ping;Zhang, Qiu-li;Hong, Lan;Liu, Li-ping;Cui, Xun;Cui, Bai-ri
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권1호
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    • pp.9-14
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    • 2016
  • Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

마우스 회장 운동에 대한 나문재 (Suaeda asparagoides MIQ) 추출물의 효과 (Effects of Suaeda asparagoides MIQ extracts on mice ileal motility)

  • 송재찬;박창희;김현탁;메하리 엔델;이만휘;박승춘;김길수;김태완
    • 대한수의학회지
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    • 제46권4호
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    • pp.323-326
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    • 2006
  • Suaeda (S.) asparagoides $M_{IQ}$, one of the halophyte groups, has been used as a folk remedy for digestive disturbances in Korea. However, its pharmacological activity on gastrointestinal motility has not been reported yet. In this study, the effects of this halophyte extracts with various solvent fractions (ethanol, hexane, chloroform, ethyl acetate, butanol, and water) on mice ileal spontaneous motility was examined. All solvent fractions at the concentration of $100{\mu}g/ml$ showed inhibitory actions on spontaneous motility of ileum with the potency order of water > 70% ethanol > hexane ${\gg}$ chloroform ${\geq}$ butanol ${\geq}$ ethyl acetate, respectively. In addition, the water fraction of extracts from S. asparagoides $M_{IQ}$ (WFSA) dose-dependently ($1-100{\mu}g/ml$) inhibited the amplitude of spontaneous phasic contraction and area under the contractile curve (AUC). The inhibitory effect of water fraction at the concentration of $10{\mu}g/ml$ was not affected by tetrodotoxin (TTX), $Na^+$ channel blocker ($1{\mu}M$), and $N^w$-nitro-L-arginine Methyl Ester (L-NAME), nitric oxide synthase inhibitor ($100{\mu}M$). However, cyclopiazonic acid (CPA, $10{\mu}M$), inhibitor of sarcoplasmic reticulum $Ca^{2+}$-ATPase, almost blocked the inhibitory effects of WFSA ($10{\mu}g/ml$) on the spontaneous phasic contraction of mouse ileum. But, CPA did not inhibit the lowering basal tone effects of WFSA. The result of this study showed that various extracts of S. asparagoides $M_{IQ}$ induce inhibitory effects on spontaneous contraction of mice ileal segments. More over, the polar solvent fractions were shown to be more potent than non-polar solvent fractions. The effects of S. asparagoides $M_{IQ}$ extracts are not mediated by nerve or nitric oxide. The inhibitory effects of WFSA at least partially mediated by sarcoplasmic reticulum $Ca^{2+}$-ATPase. However, further study is required to determine the exact pharmacological mechanisms of this halophyte on its gastrointestinal motility inhibitory effects.

Cardiovascular Responses and Nitric Oxide Production in Cerebral Ischemic Rats

  • Shinl, Chang-Yell;Lee, Nam-In;Je, Hyun-Dong;Kim, Jeong-Soo;Sung, Ji-Hyun;Kim, Dong-Seok;Lee, Doo-Won;Bae, Ki-Lyong;Sohn, Uy-Dong
    • Archives of Pharmacal Research
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    • 제25권5호
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    • pp.697-703
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    • 2002
  • We investigated that the role of nitric oxide (NO) on ischemic rats in brain and heart. Ischemia was induced by both common carotid arteries (CCA) occlusion for 24h following reperfusion. Then tissue samples were removed and measured NOx. In brain, NOx was increased by about 40% vs. normal and it was significantly inhibited by aminoguanidine, selective iNOS inhibitor. This result showed that NOx concentration was increased by iNOS. We investigated the role of $Ca^{2+}$ during ischemia. Nimodipine, L-type calcium channel blocker, didn't inhibit the increases of NOx concentration during ischemia. It suggested that increased NOx was due to calcium-independent NOS. MK-801, which N-methyl-D-aspartate (NMDA) receptor antagonist, didn't significantly prevent the increases of NOx. In heart, ischemia caused NOx decrease and it is inconsistent with NOx increase in brain. Aminoguanidine and nimodipine didnt affect on NOx decrease. But MK-801 more lowered NOx concentration than those of ischemia control group. It seemed that $Ca^{2+}$ influx in heart partially occurred via NMDA receptor and inhibited by NMDA receptor antagonist. The mean arterial pressure (MAP) in ischemic rats after 24h of CCA occlusion was decreased when compared to normal value, whereas the heart rates (HR) was not different between two groups. Aminoguanidine or MK801 had no effect on MAP or HR, but nimodipine reduced MAP. There was no difference the effects of aminoguanidine, nimodipine, or MK-801, on MAP and HR between normal rats and ischemic rats. In summary, ischemic model caused an increase of NOx concentration, suggesting that this may be produced via iNOS, which is calcium independent in brain. However in heart, ischemia decreased NOx concentration and NMDA receptor was partially involved. The basal MAP was decreased in ischemic rats but HR was not different from normal control, suggesting that increased NOx in brain of ischemic rat may result in the hypotension.

흰쥐 분리 간세포에 있어서 딜티아젬의 간클리어런스에 미치는 페노바르비탈의 영향 (Effect of Phenobarbital on the Hepatic Clearance of Diltiazem in Isolated Rat Hepatocytes)

  • 이용복;오준교;고익배
    • Journal of Pharmaceutical Investigation
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    • 제26권1호
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    • pp.33-41
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    • 1996
  • In order to study the effect of phenobarbital(PB) on the hepatic transport of diltiazem(DTZ), $Ca^{2+}$ channel blocker, we used isolated hepatocytes of rat which was intraperitoneally pretreated with phenobarbital sodium(75 mg/kg) for four days once a day. For the isolation of rat liver cells, a modification of the two step procedure of Seglen was used. DTZ was dissolved in incubation buffer to the final DTZ concentrations of 200, 400, 600, 800 and 1000 ng/ml in order to elucidate the uptake characteristics of DTZ by hepatocytes. Reactions were stopped at 10, 20, 30, 45, 60, 90, 120 and 300 sec. The initial velocity was determined by disappearance of diltiazem in the hepatocyte suspension. On the other hand, to determine the effect of PB on the in vitro hepatic intrinsic clearance of DTZ we obtained the metabolism rates of DTZ in the control and the PB-pretreated rat hepatocyte at various time intervals. According to pretreatment with PB, the size of hepatocyte and the amount of protein per $10^6$ cells were significantly (p<0.01) increased from $26.92{\pm}0.1364\;m$ to $35.31{\pm}1.00\;m$ and from $468{\pm}6.5\;{\mu}g/10^6$ cells to $628.8{\pm}12.1{\mu}g/10^6$ cells, respectively. In the case or hepatic uptake of diltiazem, $K_m$ was not different in the normalization by cell numbers and increased from $2.90\;{\mu}M\;to\;13.89\;{\mu}M$ in the normalization by protein amount. $V_max$ was increased regardless of normalization by protein amount and cell numbers, from $1.21\;{\mu}mole/min \;{\cdot}\;mg\;protein\;to\;3.96\;{\mu}mole/min\;{\cdot}\;mg\;protein\;and\;from\;2.38\;{\mu}mole/min\;{\cdot}\;10^6\;cells\;to\;2.83\;{\mu}mole/min\;{\cdot}\;10^6\;cells$, respectively. The in vitro hepatic intrinsic clearance of DTZ was significantly (p<0.01) increased from $0.640{\pm}0.038\;ml/mim\;{\cdot}\;10^6\;cells\;to\;2.385{\pm}0.212\;ml/min\;{\cdot}\;10^6\;cells$ due to PB-pretreatment. These results suggest that the uptake of DTZ by hepatocyte is extremely fast and PB enhances the hepatic intrinsic metabolic clearance of DTZ.

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폐출혈과 급속 진행성 사구체신염을 동반한 현미경적 다발성 동맥염 (Microscopic Polyangiitis) 1례 (A Case of Microscopic Polyangiitis with Pulmonary Hemorrhage and Rapidly Progressive Glomerulonephritis)

  • 권해식;이영목;김지홍;김병길;강혜윤;홍순원;정현주
    • Childhood Kidney Diseases
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    • 제5권2호
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    • pp.213-218
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    • 2001
  • 현미경적 다발성 동맥염은 폐출혈과 급속 진행성 사구체신염을 특징으로 하는 전신성 혈관염의 일종으로 소아에서 매우 드문 질환이다. 저자들은 폐출혈과 급성신부전을 동반한 7년 9개월된 여자 환아에서 신장조직 검사와 p-ANCA(perinuclear antineutrophil cytoplasmic autoantibodies) 검사로 현미경적 다발성 동맥염을 진단할 수 있었으며 이후 methyl-prednisolone pulse therapy와 cyclophosphamide, 4회의 혈장 교환 치료를 병행하였다. 환아 내원 당시 BUN 117 mg/dL, Cr 2.3 mg였으나 입원 제 60병일째 BUN 20.8 mg/dL, Cr 1.6 mg 으로 감소하고 혈뇨, 단백뇨는 지속되었으나 폐출혈 소견 호전되고 전신상태 양호하여 현재 외래 추적 관찰 중에 있다. 이에 국내외의 문헌 고찰과 함께 보고하는 바이다.

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토끼심장의 전기적 활동에 대한 갑상선 호르몬의 영향 (Effect of Thyroid Hormone on the Electrical Activity of Rabbit Heart)

  • 홍성근;권종국;정순일
    • The Korean Journal of Physiology
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    • 제20권1호
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    • pp.17-29
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    • 1986
  • 갑상선 호르몬의 표적기관(target organ) 중의 하나인 심장이 hyperthyroid상태에서 심박동수의 증가, 부정맥 그리고 세포 수들에서 sodium, potassium pump기능이 항진되는 것으로 보고되고 있다. 증진된 Pump기능과 더불어 positive chronotropic effect는 심장의 향도잡이로 알려진 동방결절 과 심방근에 어떤 변화에 의하여 발현되는지 알아보기 위하여 $3{\sim}6$개월령의 토끼 (체중 약 1.5kg내외)에 3,3',5-l-triiodothyronine$(T_3)$을 투여하며 실험적으로 hyperthyroid상태를 유도한 다음 심장세포 내에 유리미세전극을 삽입하여 기록한 결과 다음과 같은 성적을 얻었다. 1) 심박동수는 투여 전(Day 1) $169.0{\pm}28.0\;beat/min(Day\;7)$에서 $264.2{\pm}18.9\;beat/min(Day\;7)$으로 156% 가량 증가되었고 체중은 투여전 체중의 $68.2{\pm}2.0%$로 현저한 감소를 보였다. 2) $T_3$투여군에서 활동전압기간은 $148.0{\pm}29.1\;msec$에서 $107.0{\pm}13.6\;msec$로 감소하여 심박동증가를 반영하였으나 그 외의 활동전압 Parameter에서 대조군과 유의한 차를 관찰할 수 없었다. 3) 세포막에 대한 Potassium ion투과성의 영향을 알아보기 위하여 10, 15, $20mM-K^+\;Tyrode$용액을 사용한 결과 SA node에서 $15mM\;K^+$에서 활동전압 발사가 대조군에 비해 현저하게 감소하였고, 4) Ta 투여군에서 심방근의 안정막전압 탈분극 정도는 15mM(P<0.05), $20mM-K^+Tyrode$용액(P<0.05)에서 대조군보다 유의성있게 낮았다. 5) Sodium, potassium pump기능은 대조군에 비해 동방결절$(13.4{\pm}1.1\;vs.\;19.5{\pm}7.1mV,\;p<0.1)$과 심방근$(15.1{\pm}5.5\;vs.\;25.8{\pm}10.0mV,\;p<0.025)$에서 모두 높은 값을 얻었다. 6) $T_3$에 의한 calcium ion의 영향을 알아보기 위하여 $Ca^{++}\;channel\;blocker$$MnCl_2$를 사용한 결과 $T_3$ 투여군의 동방결절은 정상대조군의 것보다 낮은 농도의 $MnCl_2$ 용액에서 흥분성의 감소를 보였다.

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Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 한국균학회 2016년도 춘계학술대회 및 임시총회
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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