• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.286-286
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• 1994

Thrombin (0.25 U/ml : TB), 소-피부 collagen (200 $\mu\textrm{g}$/ml : CG), adenosine 5'-diphesphate (4,0 $\times$ $10^{-5}$M : ADP), 및 epinephrine (4,0 $\times$ 10 $^{-5}$M : EPI)의 가토-혈소판 응집과 단백인산화작용에 미치는 PDE-I (3-isobutyl-1-methylxanthine : IBMX, 및 KR 30075), amitriptyline (AP), chlorpromazine (CP), 및 sodium nitrogrosside (SNP)의 염향을 비교-검토하였다. 그 결과, KR은 2,2 $\times$ $10^{-7}$M 이하의 $IC_{50}$/에서 EPI > ADP > CG > TB 순으로 각각을 억제하였으며, SNP 보다도 강하였고; KR-30075보다 약하나 IBMX, AP, 및 CP도 각 응집재의 작용을 억제하였으며 특히 EPI에 대하여 $10^{-8}$M 이하의 $IC_{50}$/에서 유의한 억제력을 보였다. 각 응집제들은 41 kD 인산화는 유의하게 증가시키며 47 kD와 20 kD 단백인산화는 감소시켰는데; 모든 항응집성 약물이 41 kD 인산화-증가는 유의하게 억제하였다, 아울러, AP와 CP는 47 kD 단백인산화-감소에 영향을 미치지 않았으나 20 kD 단백인산화-감소는 억제하였다. PDE-I (IBMX와 KR)와 SNP는 47 kD와 20 kD 단백인산화-감소를 다소 약화시켰으며, 43 kD와 22 kD 단백인산화를 KR > IBMX > SNP순으로 유의하게 증가시켰고, KR의 22 kD 단백인산화작용은 현저하였다.

• The Korean Journal of Pain
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• v.14 no.1
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• pp.12-18
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• 2001

Background: It is controversial whether the change in nitric oxide (NO) expression in the dorsal root ganglia (DRG) may be responsible for developtment and/or maintenance of painful diabetic neuropathy. The aim of this study was to clarify the role of NO in the pathogenesis of painful diabetic neuropathy. Methods: The effect of L-nitroargine methylester (L-NAME) or sodium nitroprusside (SNP) on allodynia was measured in streptozotocin (STZ)-induced diabetic rats. NO concentration was measured in the cerebrospinal fluid (CSF) and plasma of the diabetic rats. NADPH-diaphorase (NADPH-d) histochemistry was performed on the DRG and spinal cords of the STZ-induced diabetic rats. Results: L-NAME, an inhibitor of nitric oxide synthase, alleviated allodynia, while SNP, a nitric oxide donor, aggravated allodynia in diabetic rats. Plasma NO level in the diabetic rats was significantly decreased compared with control rats. NO level in the CSF of diabetic rats did not differ from that of the control rats. NADPH-d positive cells were decreased in the DRG of diabetic rats. However, NADPH-d histochemistry in the diabetic spinal cord was not different from that of the control rats. Conclusions: Downregulation of NO expression in the diabetic rats may not be causally related to the development and/or maintenance of painful diabetic neuropathy.

• Journal of Microbiology
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• v.35 no.2
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• pp.152-157
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• 1997

Infection of human fibroblast (HF) cells with human cytomegalovirus (HCMV) result in changes in the intracellular level of second messengers. Since nitric oxide (NO) production has been known to be related with other second messengers, it is probable that HCMV infection of HF cells may involve NO. To test this possibility, the amount of NO was measured following ogenous addition of NO generators such as sodium nitroprusside (SNP) or S-nitroso-N-a-cetylpenicillamine (SNAP) immediately after HCMV infection, however, inhibited virus multiplication. Furthermore, immunoblot experiment using monoclonal antibody to HCMV major immediate early (MIE) proteins or CAT assay using pCMVIE/CAT (plasmid containing CAT gene driven by HCMV MIE promoter) revealed that SNP or SNAP blocked the MIE gene expression. SNP was more effective than SNAP in hibiting HCMV multiplication or MIE gene expression. SNP produced more NO than SNAP in inhibiting HCMV multiplication or MIE gene expression. SNP produced more NO than SNAP. Although the mechanism for the inhibition of HCMV multiplication and MIE gene expression by NO is still elusive some correlation with NO-mediated inhibition of HCMV-induced increase in cytosolic free Ca$\^$2+/ concentration ([Ca$\^$2+/]) was observed. The increase of [Ca$\^$2+/] following HCMV infection was inhibited by SNP, and less effectively by SNAP. Raising [Ca$\^$2+/ with bromo-A23187 partially reversed the SNP block of MIE gene expression. Thus, there appear to e some relationships among NO. [Ca$\^$2+/], and HCMV MIE gene expression.

• 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.

• Biomedical Science Letters
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• v.16 no.4
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• pp.259-264
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• 2010

This study was designed to investigate the effects of nitric oxide on the neuronal activity of rat cerebellar Purkinje cells. Sprague-Dawley rats aged 14 to 16 days were decapitated under ether anesthesia. After treatment with pronase and thermolysin, the dissociated Purkinje cells were transferred into a chamber on an inverted microscope. Spontaneous action potentials and potassium current were recorded by standard patch-clamp techniques under current and voltage-clamp modes respectively. 15 Purkinje cells revealed excitatory responses to $20\;{\mu}M$ of sodium nitroprusside (SNP) and 4 neurons (20%) did not respond to SNP. Whole potassium currents of Purkinje cells were decreased by SNP (n=10). Whole potassium currents of Purkinje cells were also decreased by L-arginine, substrate of nitric oxide (n=10). These experimental results suggest that nitric oxide increases the neuronal activity of Purkinje cells by altering the resting membrane potential and after hyperpolarization.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.73-77
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• 2003

The effects of nitric oxide on the vestibular function recovery following unilateral labyrinthectomy (UL) were studied. Sprague-Dawley male rats, treated with nitric oxide liberating agent sodium nitroprusside (SNP) and NOS inhibitor $N^G$-nitro-L-arginine methyl ester (L-NAME), were subjected to destruction of the unilateral vestibular apparatus, and then spontaneous nystagmus was observed in the rat. To explore the effects of nitric oxide on the neuronal excitability, whole cell patch clamp technique was applied on isolated medial vestibular nuclear neurons. The frequency of spontaneous nystagmus in SNP treated rats was lesser than that of spontaneous nystagmus in control animals. In contrast, pre-UL treatment with L-NAME resulted in a significant increase in spontaneous nystagmus frequency. In addition, SNP increased the frequency of spontaneous action potential in isolated medial vestibular nuclear neurons. Potassium currents of the vestibular nuclear neurons were inhibited by SNP. After blockade of calcium dependent potassium currents by high EGTA (11 mM) in a pipette solution, SNP did not inhibit outward potassium currents. 1H-[1,2,4] oxadiazolo [4,3-a] quinozalin-1-one (ODQ), a specific inhibitor of soluble guanylyl cyclase, inhibited the effects of SNP on the spontaneous firing and the potassium current. These results suggest that nitric oxide after unilateral labyrinthectomy would help to facilitate vestibular compensation by inhibiting calcium-dependent potassium currents through increasing intracellular cGMP, and consequently would increase excitability in ipsilateral vestibular nuclear neurons.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.93-98
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• 2001

The precise mechanism of set-point regulation in hypothalamus was not elucidated. Nitric oxide synthases(NOS) were detected in hypothalamus, however, the roles of NO in hypothalamus was not fully studied. So, we tested the effects of NO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. NO donor sodium nitroprusside (SNP, 4 nmol, i.c.v.) elicited marked febrile response, and this febrile response was completely blocked by indomethacin (a cyclooxygenase inhibitor). But, ODQ (selective guanylate cyclase inhibitor, $50\;{\mu}g,$ i.c.v.) did not inhibit fever induced by SNP. The cyclic GMP analogue dibutyryl-cGMP $(100\;{\mu}g,\;i.c.v.)$ induced significant pyreses, which is blocked by indomethacin. $N^G-nitro-L-arginine$ methyl ester (L-NAME, non selective NOS inhibitor) inhibited fever induced by $interleukin-1{\beta}\;(IL-1{\bata},\;10\;ng,\;i.c.v.),$ one of endogenous pyrogens. These results indicate that NO may have an important role, not related to stimulation of soluble guanylate cyclase, in the signal pathway of thermoregulation in hypothalamus.

• Development and Reproduction
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• v.1 no.2
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• pp.165-172
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• 1997

the pupose of this study was to investigate the effects of gonadotropin and nitric oxide (NO) on the expression of mouse follicular bad and bax genes that are known induce apoptosis. Large and midium size follicles of immature mice were obtained at 0, 24, and 48 hours time intervals after Pregnant Mare's Serum gonadotropins(PMSG, 5 I.U.) injection. Preovulatory follicles collected at 24 hrs after PMSG injection were cultured with or without various chemicals such as gonadotropin, gonadotropin Releasing hormone(GnRH), testosterone, Sodium nitroprusside (SNP) for 24 hrs at $37^{\circ}C$. After 24 hrs culture, the culture media was used for nitrite assay and total RNA was extracted, subjected to RT-PCT for the analyses of bad and bax expression. We found that expression of bad and bax genes in follicles was markedly reduced before and after in vivo priming with hCG. When the preovulatory follicles were cultured for 24 hrs in culture media with PMSG and hCG, the expression of bad and bax genes was decreased. Moreover, SNP (NO generating agent) can significantly suppress the expression of bad and bax genes in follicles when apoptosis was induced by GnRH agonist and testosterone. At the same time, nitrite production of culture media was increased in GnRH agonist + SNP, testosterone + SNP and SNP treated groups than control group. These data demonstrated for the first time that peptide hormones and NO may play important roles in the regulation of mouse follicular differentiation and may prevent apoptosis via supressing the expression of bad and bax genes.

• Journal of Life Science
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• v.20 no.10
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• pp.1443-1450
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• 2010

Honokiol is a small molecular weight ligand originally isolated from the Chinese medicinal herb Magnolia officinalis, a plant used in traditional Chinese and Japanese medicine [9]. In a previous study, the effects of honokiol were shown to have anti-angiogenic, anti-invasive and anti-proliferative activities in a variety of cancers [1,3,4,11,13,17,24,29,30]. We showed previously that direct production of nitric oxide (NO) by treatment of NO donor, sodium nitroprusside (SNP), led to apoptosis in rabbit articular chondrocytes [15,16]. This study confirmed that NO-induced apoptosis was suppressed by honokiol treatment in a dose-dependent manner as determined by cell phenotype, MTT assay, Western blot analysis and FACS analysis in articular chondrocytes. Treatment of honokiol inhibited SNP-induced expression of p53 as well as DNA fragmentation in articular chondrocytes, but increased expressionof pro-caspase-3. Inhibition of SNP-induced apoptosis by honokiol treatment was rescued by LY294002, the specific inhibitors of phosphoinositide 3-kinase (PI-3K) in articular chondrocytes. Our results indicate that honokiol inhibits NO-induced apoptosis via PI-3K/AKT pathway in rabbit articular chondrocytes.

• Korean Journal of Food Science and Technology
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• v.40 no.6
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• pp.696-701
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• 2008

The objective of this study was to determine whether Codonopsis lanceolata or Platycodon grandiflorum ethyl acetate fraction (CLEA or PGEA) protect cells against sodium nitroprusside (SNP)-induced oxidative stress via the expression of various antioxidant systems. The HepG2 cells exposed for 24 hr to 0.5 mM SNP showed a reduction in the cell viability by an MTT assay. Pretreatment with CLEA and PGEA resulted in an inhibition of SNP-induced cell death. In addition, the effects of CLEA and PGEA on the expression of antioxidant systems via RT-PCR analyses was assessed. The levels of catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD) and metallothionein (MT)-1A mRNA were increased after 24 hr of CLEA exposure. The levels of Mn superoxide dismutase CAT, G6PD, MT-1A, and MT-2A mRNA were increased after PGEA treatment. In conclusion, CLEA and PGEA exert indirect antioxidant effects, perhaps via the induction of a variety of antioxidant systems which, may protect cells against oxidative stress.