• Applied Microscopy
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• v.18 no.2
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• pp.34-46
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• 1988

The stimulation-secretion coupling in the pancreatic acinar cell have been studied by electron microscope. Morphological changes in the cells exhibited the cellular response induced by acetylcholine and MNNG. MNNG, a guanylate cyclase activator, induced the formation of numerous secretory granules in a period after the agent administration. This result suggest that guanylate cyclase potentiated the early sustained response in pancreatic acinar cells stimulated by acetylcholine. Cycloheximide and dibucaine reduced the secretory granules in number during sustained period. In pancreatic acinar cells, the secretion granules were considered to be directly packaged from cisternal space of endoplasmic reticulum.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.471-477
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• 1998

Cyclosporin A (CsA), a widely used immunosuppressant, is well known to cause nephrotoxicity and hypertension as major side effects. The present study was aimed at investigating the effects of CsA-pretreatment on the activities of cytosolic guanylate cyclase (cGC) in relation to the alteration of relaxant responses in the rat thoracic aorta. CsA $(10\;{\mu}M)-preincubation$ for 90 min significantly attenuated the vasodilatation induced by sodium nitroprusside (SNP), a cytosolic guanylate cyclase activator, shifting the dose-response curve to the right. The increase in cGMP contents induced by SNP was markedly attenuated by CsA. SNP ($1\;{\mu}M{\sim}\;mM$) increased the cGC activity dose-dependently, and the increase was completely abolished by CsA. CsA attenuated the SNP-induced cGC activation dose-dependently. The abolishing effect of CsA-pretreatment on the SNP-induced cGC activation was not affected by washing the preparation, suggesting that the inhibition is irreversible. When CsA was added simultaneously with SNP, cGC activation was not attenuated. 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine (H-7), a protein kinase C (PKC) inhibitor, decreased SNP-induced cGC activation and blocked the CsA-attenuation of cGC activation. These results suggest that CsA directly inhibits cGC participating in the CsA-induced impairment of vasodilatation, and that PKC is involved in the inhibitory action of CsA on cGC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.783-788
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• 2004

Cheonmabanhwa- Tang (CBT) has been used in the Oriental Medicine for many centuries as a therapeutic agent for dizziness due to Poong-Dam, We reported that CBT had effects on the cerebral hemodynamics [regional cerebral blood flow (rCBF), pial arterial diameter (PAD), and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats. Therefor we designed to determine the mechanism of action of CBT. The changes of rCBF and MABP were determinated by laser-Doppler flowmetry(LDF), and the change of PAD was determinated by video-microscopy. The results were as follows: The CBT-induced increase in rCBF was significnatly inhibited by pretreatment with indomethacin (IDN, 1 ㎎/㎏, i.p.), an inhibitor of cyclooxygenase, or methylene blue (MTB, 10 ㎍/㎏, i.p.), an inhibitor of guanylate cyclase. The CBT-induced increase in PAD was also significantly inhibited by pretreatment with IDN or MTB. The CBT-induced increase in MABP was also significantly inhibited by pretreatment with IDN or MTB. In conclusion, it is suggested that CBT causes a diverse effect on cerebral hemodynamics via mediation of cyclooxygenase and guanylate cyclase.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.343-351
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• 2001

This study was undertaken to investigate the mechanism of lipopolysaccharide (LPS) and nitric oxide (NO) as a regulator of vascular smooth muscle cell (VSMC) proliferation. VSMC was primarily cultured from rat aorta and confirmed by the immunocytochemistry with anti-smooth muscle myosin antibody. The number of viable VSMCs were counted, and lactate dehydrogenase (LDH) activity was measured to assess the degree of cell death. Concentrations of nitrite in the culture medium were measured as an indicator of NO production. LPS was introduced into the medium to induce the inducible nitric oxide synthase (iNOS) in VSMC, and Western blot for iNOS protein and RT-PCR for iNOS mRNA were performed to confirm the presence of iNOS. Inhibitors of iNOS and soluble guanylate cyclase (sGC), sodium nitroprusside (SNP) and L-arginine were employed to observe the action of LPS on the iNOS-NO-cGMP signalling pathway. LPS and SNP decreased number of VSMCs and increased the nitrite concentration in the culture medium, but there was no significant change in LDH activity. A cell permeable cGMP derivative, 8-Bromo-cGMP, decreased the number of VSMCs with no significant change in LDH activity. L-arginine, an NO substrate, alone tended to reduce cell count without affecting nitrite concentration or LDH level. Aminoguanidine, an iNOS specific inhibitor, inhibited LPS-induced reduction of cell numbers and reduced the nitrite concentration in the culture medium. LY 83583, a guanylate cyclase inhibitor, suppressed the inhibitory actions of LPS and SNP on VSMC proliferation. LPS increased amounts of iNOS protein and iNOS mRNA in a concentration-dependent manner. These results suggest that LPS inhibits the VSMC proliferation via production of NO by inducing iNOS gene expression. The cGMP which is produced by subsequent activation of guanylate cyclase would be a major mediator in the inhibitory action of iNOS-NO signalling on VSMC proliferation.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.305-308
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• 2007

Vasoplegic syndrome occurs in $8{\sim}10%$ of patients following cardiac surgery, and this happens in part because of inducing the inflammatory response. Nitric oxide and guanylate cyclase play an important role in this response, and this is associated with increased morbidity and mortality. For our case, we administered methylene blue (MB), an inhibitor of guanylate cyclase, early after performing cardiopulmonary bypass in a patient with vasoplegic syndrome. The patient recovered immediately after MB administration and maintained an optimal blood pressure without the aid help of any vasopressors.

• Molecules and Cells
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• v.44 no.7
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• pp.529-537
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• 2021

Most animals face frequent periods of starvation throughout their entire life and thus need to appropriately adjust their behavior and metabolism during starvation for their survival. Such adaptive responses are regulated by a complex set of systemic signals, including hormones and neuropeptides. While much progress has been made in identifying pathways that regulate nutrient-excessive states, it is still incompletely understood how animals systemically signal their nutrient-deficient states. Here, we showed that the FMRFamide neuropeptide FLP-20 modulates a systemic starvation response in Caenorhabditis elegans. We found that mutation of flp-20 rescued the starvation hypersensitivity of the G protein β-subunit gpb-2 mutants by suppressing excessive autophagy. FLP-20 acted in AIB neurons, where the metabotropic glutamate receptor MGL-2 also functions to modulate a systemic starvation response. Furthermore, FLP-20 modulated starvation-induced fat degradation in a manner dependent on the receptor-type guanylate cyclase GCY-28. Collectively, our results reveal a circuit that senses and signals nutrient-deficient states to modulate a systemic starvation response in multicellular organisms.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.303-313
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• 1997

The role of the lower esophageal sphincter(LES) is characterized by the ability to maintain tone and to relax allowing the passage of a bolus. It is known that LES relaxation during swallowing may be induced by the cessation of the tonic neural excitation and the activation of non-adrenergic, non-cholinergic(NANC) inhibitory neurons. Furthermore, it is generally accepted that the relaxation of the smooth muscle is mediated primarily by the elaboration of adenosine 3',5'-cyclic monophosphate(cyclic AMP) and guanosine 3',5'-cyclic mono-phosphate(cyclic GMP) via activation of adenylate cyclase and guanylate cyclase, respectively. It is thus possible that cyclic nucleotides might be a second messenger involved in neural stimulation-induced relaxation of LES, although a relationship between relaxation and changes in cyclic nucleotides after neural stimulation has not been established. The present study was performed to define the participation of cyclic nucleotides in the relaxation of LES of dog in response to neural stimulation. Electrical field stimulation(EFS) caused relaxation of the canine isolated LES strips in a frequency-dependent manner, which was eliminated by pretreatment with tetrodotoxin$(1{\mu}M)$, but not by atropine$(100{\mu}M)$, guanethidine$(100{\mu}M)$ and indomethacin$(10{\mu}M)$. The nitric oxide synthase inhibitors, $N^G-nitro-L-arginine$, $N^G-nitro-L-arginine$ methyl ester and $N^G-monomethyl-L-arginine$ inhibited EFS-induced relaxation. Additions of sodium nitroprusside, a nitrovasodilator and forskolin, a direct adenylate cyclase stimulant, caused a dose-dependent relaxation of LES smooth muscle. Effects of sodium nitroprusside and forskolin were selectively blocked by the corresponding inhibitors, methylene blue for guanylate cyclase and N-ethylmaleimide(NEM) for adenylate cyclase, respectively. Dibutyryl cyclic AMP and dibutyryl cyclic GMP caused a concentration-dependent relaxation of the LES smooth muscle tone, which was not blocked by NEM or methylene blue, respectively. However, both NEM and methylene blue caused significant antagonism of the relaxation in LES tone in response to EFS. EFS increased the tissue cyclic GMP content by 124%, whereas it did not affect the tissue level of cyclic AMP. Based on these results, it is suggested that one of the components of canine LES smooth muscle relaxation in response to neural stimulation is mediated by an increase of cyclic GMP via the activation of guanylate cyclase. Additionally, an activation of cyclic AMP generation system was, in part, involved in the EFS-induced relaxation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.50-56
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• 2009

The present study was designed to investigate the effects of Phamacopuncture therapy using Cervi Pantotrichum Cornu (PC) at BL23 BL52 on the regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, then the related mechanisms were also investigated. In addition, the present author also investigated the effects of phamacopuncture therapy at BL23.BL52 on the rCBF in cerebral ischemic rats. The results in normal rats were as follows; PC (3 mg/kg and 5 mg/kg) at BL23 BL52 significantly increased rCBF but decreased MABP. This result suggests that PC at BL23 BL52 significantly increased rCBF by dilating pial arterial diameter. Increase of PC (5 mg/kg)-induced rCBF was significantly inhibited by pretreatment with indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue ($10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. Decrease of PC (5 mg/kg)-induced MABP was significantly increased by pretreatment with methylene blue but was decreased by pretreatment with indomethacin. These results suggested that the action of PC (5 mg/kg) was mediated by guanylate cyclase. The results in cerebral ischemic rats were as follows ; The rCBF was significantly and stably increased by PC (5 mg/kg) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in Control group. In conclusion, these results suggest that phamacopuncture therapy using Carthami flos at BL23 BL52 can increase rCBF in normal state, and improve stability of rCBF in ischemic state. In addition, the present author also suggest that related mechanisms are involved in guanylate cyclase pathway.

• 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.

• 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.