• Journal of Acupuncture Research
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• v.26 no.2
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• pp.31-40
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• 2009

Objectives: The purpose of this study is to investigate the effects of Daedon($LR_1$) Supplementation and Eumgok($KI_{10}$) Draining on changes of cerebral blood flow in normal rats. Methods : Regional cerebral blood flow(rCBF) and mean arterial blood pressure(MABP) in normal rats are observed, and those mechanisms were also investigated with pre-treatment of indomethacin (IDM) and methylene blue(MTB) each. Results : In this study, $LR_1$ supplementation and $KI_{10}$ draining elevated level of rCBF after 30 min, but MABP level was lowered at 30 min, then recovered toward normal level. Pre-treatment with indomethacin (IDM), an inhibitor of cyclooxygenase, inhibited increase of rCBF effectively, and pre-treatment with methylene blue(MTB), an inhibitor of guanylate cyclase, also inhibited increase of rCBF levels. On the other hand pre-treatment with IDM or MTB did not affect MABP levels. Conclusions : In conclusion, these results suggest that $LR_1$ supplementation and $KI_{10}$ draining can increase rCBF, and the mechanisms are thought to be related to both of cyclooxygenase and Guanylate cyclase pathways.

• Korean Journal of Veterinary Research
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• v.22 no.1
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• pp.1-8
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• 1982

The effect of acetylcholine, oxytocin and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) on cyclic nucleotide levels in estrogen-primed rabbit whole uterus were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiestrase inhibitor, and indomethacin, a prostagandin inhibitor. In the absence of MIX, acetylcholine increased guanosine 3', 5'-cyclic monophosphate (cGMP), but had no effect on adenosine 3', 5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin had no influence on cGMP, but decreased cAMP levels. $PGF_{2{\alpha}}$ increased cGMP and decreased cAMP levels. MIX increased both cAMP and cGMP levels. Oxytocin and $PGF_{2{\alpha}}$ further increased cGMP levels, indicating activation of guanylate cyclase activity. The ratio of cAMP/cGMP was decreased by uterine stinulants both in presence and absence of MIX. Indomethacin elevated cAMP and cGMP revels. The effects of uterine stimulants in the presence of indomethacin on cyclic nucleotide levels were varied from tissue to tisse. In general, oxytocin decreased cGMP and $PGF_{2{\alpha}}$ increased cAMP/cGMP levels, but the effects were statisically nonsignicficant. The cAMP/cGMP ratio was increased by uterine stimulant in the presence of indomethacin. In conclusion, uterine stimulants eased cAMP/cGMP ratio which indicates that the uterine stimulants have opposing effects on adenylate cyclase and guanylate cyclase activities. The endometrium plays a role in the regulation of cyclic nucleotide levels and uterine contraction by means of PG synthesis. Indomethacin has an unknown activities besides both of PG synthetase and phosphodiesterase inhibitions.

• Journal of Acupuncture Research
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• v.28 no.4
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• pp.19-35
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• 2011

Objectives : This study was designed to investigate the effects of acupuncturing $PC_8$ used perpendicular needling method determine the mechanism of action of acupuncturing $PC_8$ by measuring the changes of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats. Methods : This study also investigated the effects of acupuncturing $PC_8$ on the change of rCBF in cerebral ischemic rats, and revealed the mechanism of its action. In addition, the effects of acupuncturing $PC_8$ on focal ischemic brain injury was studied in cerebral ischemic rats. Results : 1. Acupuncturing $PC_8$ significantly increase rCBF but decreased MABP in normal rats. 2. Acupuncturing $PC_8$ increased of rCBF was significantly inhibited by pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase in normal rats. 3. Acupuncturing $PC_8$ increased of rCBF was significantly inhibited by pretreatment methylene blue (10 ${\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase in normal rats. 4. Acupuncturing $PC_8$ was significantly improved the rCBF than control group increased unstable in cerebral ischemic rats. 5. Acupuncturing $PC_8$ was not significantly improved the rCBF than control group by pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase in cerebral ischemic rats. 6. Acupuncturing $PC_8$ was significantly increased the rCBF than control group by pretreatment methylene blue ($10{\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase in cerebral ischemic rats. Conclusions : In conclusion, our study suggested that acupuncturing $PC_8$ can increase rCBF in normal state, and improve stability of rCBF in ischemic state. In addition, we suggested that mechanisms related with acupuncturing $PC_8$ was involved in the guanylate cyclase pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.173-182
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• 2013

This Study was designed to investigate the effects of Sibjeondaebo-tang (SDT) and Gamy-Sibjeondaebo-tang (GST, Sibjeondaebo-tang adding Cervi Pantotrichum Cornu) on the improvement in regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and in the rats with cerebral ischemia induced by middle cerebral artery occlusion, and further to determine the mechanisms. And, It was to investigate the effects of the SDT and GST with the change of histologic examination through the BDNF in the hippocampus CA1. In changes of cerebral hemodynamics, SDT and GST significantly increased rCBF in a dose-dependent manner but decreased MABP in normal rats. In mechanism of cerebral hemodynamics, Increase of GST-induced rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, i.p.), an inhibitor of guanylate cyclase, and Decrease of GST-induced MABP was significantly increased by pretreatment with methylene. These results suggested that the action of GST was mediated by guantlate cyclase pathway. In cerebral ischemics, the rCBF was stably improved by SDT (10 mg/kg, i.p.) significantly and stably increased by GST (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrast with the findings of rapid and marked increase in Control group. These results suggested that GST had anti-ischemic action in cerebral ischemic state. In histological examination through TTC stain, Sample A group and Sample B group decreased discoloration in the cortical part at $28^{th}$ day after MCAO induction. In immunohistochemistric response of BDNF, Sample A group and Sample B group increased respondent effect at $28^{th}$ day after MCAO induction. These results suggest that GST can Increase rCBF in normal state, as well as improve the stability of rCBF in cerebral ischemic state. Furthermore, methylene blue inhibitor study suggested the mechanism of blood flow enhancement by GST may be mediated by guanylate cyclase pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.13-17
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• 1997

Carbamazepine (CBZ), an anticonvulsant, has beeen reported to displace ligands at adenosine receptors. Several studies have demonstrated that as far as $A_2$adenosine receptors is concerned, CBZ acts as an antagonist. However, the situation with regard to Al receptors is less straightforward. In this study, we describe the effects of one-week CBZ treatment (25 mg/kg/day) on cerebrocortical $A_1$ adenosine receptors. $A_1$ adenosine receptor bindings as determined by using $[^3CH]DPCPX$ was not significantly altered in membranes prepared from CBZ-treated rats. However, there was a significant decrease in the $A_1$ adenosine receptor-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ binding to cerebrocortical membranes prepared from CBZ-treated rats (20.0% decrease in basal activity; 17.8% decrease in maximal activity). The basal and $10^{-4}$ M forskolin-stimulated adenylyl cyclase activities were relatively unaffected by CBZ treatment, but 10 mM NaF-stimulated adenylyl cyclase activity was significantly reduced in CBZ-treated rats. It appears that one-week CBZ treatment caused an uncoupling of adenosine receptors from G proteins without alteration of $A_1$ adenosine receptor molecules, suggesting that CBZ acts as an agonist at $A_1$ adenosine receptors in rat brain.

• Journal of Plant Biotechnology
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• v.30 no.2
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• pp.201-206
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• 2003

Differential responses of red pepper plant and cultured cells to enhanced ${\gamma}$-ray($^{60}$ Co) and ultraviolet(UV) stress were investigated. In seed treatment, 1 Gy of ${\gamma}$-ray increased seedling dry weight up to 19.1%, but 50 Gy treatment markedly ingibited seed germination and subsequent growth of seedling. UV treatment to seed did not change the germination ability of seeds and the growth of seedlings regardless of duration of UV treatment until 24 hrs. In case of UV treatment to seedlings, plant injury was seriously progressed even after the seedlings were returned to no UV condition, and eventually all the leaves showed chlorosis by the stress. However, progress of plant injury by ${\gamma}$-ray stress slower than that caused by UV stress, and even at the high dose of ${\gamma}$-ray 50 Gy, did not caused the cholrosis of stressed plant leaf. Amount of electrolytes leakage from plant leaf by UV treatment for 24hrs was increased up to 28.8 folds in comparison with untreated control, whereas that of 50 Gy of ${\gamma}$-ray was increased only 1.2 folds. UV stress induced the production of capsidiol, antimicrobial phytoalexin, by activation of gene expression involved in capsidiol biosynthesis, such as sesquiterpene cyclase and cyclase and cytochrome P450 hydroxylase in the leaf and cultured cell, but ${\gamma}$-ray stress induced neither the production of capsidiol nor expression of the genes.

• Journal of Microbiology
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• v.43 no.3
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• pp.313-318
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• 2005

In this study, we demonstrate the use of a PCR-based method for the detection of the specific genes involved in natural-product biosynthesis. This method was applied, using specifically designed PCR primers, to the amplification of a gene segment encoding for sedo-heptulose 7-phosphate cyclase, which appears to be involved in the biosynthetic pathways of $C_7N$ aminoacyclitol or its keto analogue-containing metabolites, in a variety of actinomycetes species. The sequences of DNA fragments (about 540 bp) obtained from three out of 39 actinomycete strains exhibited a high degree of homology with the sedo-heptulose 7-phosphate cyclase gene, which has been implicated in acarbose biosynthesis. The selective cultivation conditions of this experiment induced the expression of these loci, indicating that the range of $C_7N$ aminoacyclitol or its keto analogue-group natural products might be far greater than was previously imagined. Considering that a total of approximately 20 $C_7N$ aminoacyclitol metabolites, or its keto analogue-containing metabolites, have been described to date, it appears likely that some of the unknown loci described herein might constitute new classes of $C_7N$ aminoacyclitol, or of its keto analogue-containing metabolites. As these metabolites, some of which contain valienamine, are among the most potent antidiabetic agents thus far discovered, the molecular detection of specific metabolite-producing actinomycetes may prove a crucial step in current attempts to expand the scope and diversity of natural-product discovery.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.75-83
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• 2004

This experimental study was designed to investigate the effects of Sagunja-tang(SGJT), Ijin-tang(IJT), Yukgunja-tang(YGJT) on the change of cerebral hemodynamics [regional cerebral blood f1ow(rCBF), mean arterial blood pressure(MABP), and pial arterial diameter (PAD)] in normal rats, and further to determine the mechanism of action of YGJT. And, this Study was designed to investigate whether YGJT inhibit lactate dehydrogenase(LDH) activity in neuronal cells. The results were as follows ; 1. SGJT significantly increased rCBF but MABP was not changed comparing with normal MABP(l00 %). This results were suggested that SGJT significantly increased rCBF by dilating PAD. 2. IJT significantly decreased rCBF in a dose-dependent, but significantly increased MABP in a dose-dependent. This results were suggested that IJT significantly decreased rCBF by contracting PAD. 3. YGJT significantly increased rCBF and PAD in a dose-dependent, and YGJT increased MABP compared with normal MABP(100 %). This results were suggested that YGJT significantly increased rCBF by dilating PAD. 4. The YGJT-induced increase in rCBF was significantly accelerated by pretreatment with indomethacin (IDN, 1 mg/kg, i.p.), an inhibitor of cyclooxygenase but was significantly inhibited by methylene blue (MTB, 10 ㎍/㎏ i.p.), an inhibitor of guanylate cyclase. 5. The YGJT-induced increase in PAD and MABP were accelerated by pretreatment with IDN but was significantly inhibited by MTB. This results suggested that the mechanism of YGJT is mediated by guanylate cyclase. 6. YGJT inhibited significantly LDH activity in neuronal cells. This results were suggested that YGJT prevented the neuronal death. I thought that YGJT should have improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.325-331
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• 2000

The present study was designed to assess the role of spinal adenosine $A_2$ receptor in the regulation of cardiovascular functions such as mean arterial pressure (MAP) and heart rate (HR) in male Sprague-Dawley rats. Rats (250~300 g) were anesthetized with urethane and paralyzed with d-tubocurarine and artificially ventilated. blood pressure and HR were continuously monitored via a femoral catheter connected to a pressure transducer and a polygraph. Drugs were administered intrathecally using injection cannula through guide cannula which was inserted inthrathecally at lower thoracic level through a puncture of an atlantooccipital mombrane. Intrathecal injection of an adenosine $A_2$ receptor agonist, 5'-(N-cyclopropyl)-carboxamaidoadenosine (CPCA; 1, 2 and 3 nmol, respectively), produced a dose-dependent decrease in MAP and HR. Pretreatment with $N^{G}$-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or 10 nmol of MDL-12,330, an adenylate cyclase inhibitor blocked significantly the depressor and bradycardic effect of 2 nmol of CPCA. But, Pretreatment with 3 nmol of bicuculline, gamma-aminobutyric acid A (GAB $A_{A}$) receptor antagonist, or 50 nmol of 5-aminovaleric acid, GAB $A_{B}$ receptor antagonist did not inhibit the depressor and bradycardic effect of 2 nmol of CPCA. These results indicate that adenosine $A_2$ receptor in the spinal cord plays an inhibitory role in the regulation of cardiovascular function and that the depressor and bradycardic action of adonosine $A_2$ receptor are mediated via the synthesis of nitric oxide and the activation of adenylate cyclase in the spinal cord of rats.s.s.s.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.151-158
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• 1996

Following the subcutaneous administration of $R(-)N^6-(2-phenylisopropyl)adenosine(600\;nmol/kg/hr)$ to rats for 1 week using t$Alzet^{\circledR}$ mini-osmotic pumps, $A_1$ adenosine receptor functions were determined using $[^3H]DPCPX$ binding, $[^{35}S]GTP_{\gamma}S$ binding, and adenylyl cyclase assays. $A_1$ adenosine receptor binding and the inhibition of adenylyl cyclase activity by PIA was not altered in cerebrocortical membranes prepared from PIA-treated rats. However, there was a significant decrease in the $A_1$ adenosine receptor-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ binding to cerebrocortical membranes prepared from PIA-treated rats(22.0% decrease in basal activity; 19.7% decrease in maximal activity). These results suggest that the desensitization of $A_1$ adenosine receptors following chronic administration involves agonist-induced uncoupling of the receptors from G proteins rather than alteration of $A_1$ adenosine receptor molecules. It is also suggested that the determination of stimulation of $[^{35}S]GTP_{\gamma}S$ binding to G proteins is a suitable tool in studying the receptor regulation including desensitization