• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1065-1072
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• 2004

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.209-217
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• 2001

This study was attempted to investigate on renal effect of ($\pm$)6-chloro-7,8-dihydroxy-1-phenol 2,3,4,5-tetrahydro-lH-3 benzazepine (SKF 81297), dopamine $D_1$ receptor agonist, in dog. SKF 81297, when gluten intravenously, produced diuretic action along with the increases of renal plasma flow (RPF), glomerular filtration rate (GFR), amounts of N $a^{+}$ and $K^{+}$ excreted into urine ( $E_{Na}$ , $E_{K}$) and osmolar clearance ( $C_{osm}$). It also decreased the reabsorption rates of N $a^{+}$ and $K^{+}$ in renal tubule ( $R_{Na}$ , $R_{K}$) and free water clearance ( $C_{H2O}$), whereas ratios of $K^{+}$ agonist N $a^{+}$ in urine and filtration fraction (FF) was not changed. SKF 81297, when administered into a renal artery, elicited diuresis both in experimental kidney given the SKF 81297 and control kidney not given, while the effect was more remarkable in experimental kidney than those exhibited in control kidney. SKF 81297 given into carotid artery also exhibited diuresis, the potency at this time, compared to those induced by intravenous SKF 81297, was magnusgreat. Above results suggest that SKF 81297 produces diuresis by both indirect action through changes of central function and direct action being induced in kidney. Central diuretic action is mediated by improvement of renal hemodynamics, but direct action by inhibition of electrolytes reabsorption in renal tubule.enal tubule. tubule.

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.112-115
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• 2000

A synthetic procedure for the preparation of indole-2,3-dione derivatives 6 as a potential NMDA receptor glycine site antagonist with improved pharmacological profile compared with 2-carboxyindole derivative 5, starting from readily available 3,5-dichloroaniline (7), is described.

• 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.

• YAKHAK HOEJI
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• v.43 no.5
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• pp.642-651
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• 1999

Nonsedating antihistamines do net cause sedation in therapeutic doses because these drugs hardly cross the blood-brain barrier. Since most of the peripheral side dffects of conventional antihistamines are related to their muscarinic receptor blocking action, the present study was performed to investigate whether nonsedating antihistamines interact with the muscarinic receptors and discriminate the muscarinic receptor subtypes in the rat cerebral microsomal fraction which containes both $M_1,{\;}M_2,{\;}M_3{\;}and{\;}M_4$ receptors. Five nonsedating antihistamines at high concentrations inhibited [$^3H$]QNB binding to the muscarinic receptor in a dose-dependent manner. The inhibition curves of these drugs except loratadine which showed positive cooperativity (nH=1.55) were steep (nH=1), indicating interaction with a single homogenous population of the binding sites. Astemizole, clemizole and mequitazine increased the $K_D$ value for [$^3H$]QNB without affecting the binding site concentrations, and this increase in the $K_D$ value resulted from the ability of these drugs to slow [$^3H$]QNB-receptor association. The Ki values of astemizole, clemizole and mequitazine for the inhibition for the inhibition of [$^3H$]QNB binding to muscarinic receptor were 0.58, 5.99 and $0.007{\;}{\mu}M$, respectively. However, loratadine and terfenadine inhibited noncompetitively [$^3H$]QNB binding with the normalized $IC_50$ value of about $2{\;}{\mu}M$. These results demonstrate that; 1) astemizole, clemizole and mequitazine interact directly with the muscarinic receptor at high concentrations; 2) muscarinic receptor blocking potency of these drugs varies widely among drugs; 3) these drugs do not discriminate between muscarinic receptor subtypes.

• Biomedical Science Letters
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• v.13 no.4
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• pp.333-339
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• 2007

Recently, much attention has been paid to human retinoblastoma since it provide a good model system for studying mechanisms underlying cell growth, differentiation, proliferation, and apoptosis, and for developing cancer therapy. However, until now it is unclear whether purinergic receptors are involved in the calcium mobilization in the retinoblastoma cells. In this regard, we measured possible purinergic signaling in WERI-Rb-1 cells using $Ca^{2+}$ imaging technique and RT-PCR method. ATP-induced $[Ca^{2+}]_i$ transients was maintained to about $90.7{\pm}1.0%$ of the control (n=48) even in the absence of extracellular calcium. The ATP-induced intracellular calcium response was only attained to $10.4{\pm}1.8%$ (n=55) of peak amplitude of the control after preincubation of 1 ${\mu}MU-73122$, a PLC inhibitor, but it was not affected by 1 ${\mu}MU-73343$, a inactive form of U-73122. And also ATP-induced $[Ca^{2+}]_i$ rise was almost attenuated by 20 ${\mu}M$ 2-APB, a putative $IP_3$ receptor inhibitor. Two subtypes of $IP_3$ receptor $(IP_{3-1}R,\;IP_{3-2}R)$ were identified by a RT-PCR method. These findings suggest that purinergic stimuli can cause calcium mobilization via $PLC-IP_3$ pathway after the activation of P2Y receptors in the retinoblastoma cells, which may play important roles in cell proliferation, differentiation, growth, and cell death.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.253.1-253.1
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• 2003

Twenty-seven N,N',N"-trisubstituted thiourea derivatives were prepared. Among them, 1- [3-(4'-hydroxy-3'-methoxy-phenyl)-propyl] -1,3-diphenethyl-thiourea (81, IC$\sub$50/= 0,32 $\mu\textrm{m}$), showed 2-fold higher antagonistic activity than that of capsazepine (3, IC$\sub$50/= 0,65 $\mu\textrm{m}$) against the vanilloid receptor in a Ca$\^$2+/ -influx assay.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.540-548
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• 2018

Background: Acute hepatic failure is a life-threatening critical condition associated with rapid deterioration of liver function and liver transplantation. Several studies have shown that Panax ginseng Mayer has antidiabetic and hepatoprotective effects. However, the hepatoprotective effect of ginseng berry is still unveiled. In this study, we evaluated the hepatoprotective effects of ultrasonication-processed ginseng berry extract (UGBE) on acute hepatic failure model in rats. Methods: Ginseng berry extract (GBE) was ultrasonically processed. The GBE, silymarin, and UGBE were orally administered to male Sprague-Dawley rats for 4 wk. Twenty-four h after the last administration, rats were challenged with D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Results: After ultrasonication, the component ratio of ginsenosides Rg2, Rg3, Rh1, Rh4, Rk1, Rk3, and F4 in GBE had been elevated. Administration of UGBE significantly increased the survival rate of D-GalN/LPS-challenged rats. Pretreatment with UGBE significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in D-GalN/LPS-challenged rats in a dose-dependent manner. The levels of enzymatic markers for oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and glutathione) were increased by UGBE treatment in a dose-dependent manner. Tumor necrosis factor alphalevel, inducible nitric oxide synthase activities, and nitric oxide productions were reduced by UGBE treatment. In addition, hemeoxygenase-1 levels in liver were also significantly increased in the UGBE-treated group. The protein expression of toll-like receptor 4 was decreased by UGBE administration. Hematoxylin and eosin staining results also supported the results of this study showing normal appearance of liver histopathology in the UGBE-treated group. Conclusion: UGBE showed a great hepatoprotective effect on D-GalN/LPS-challenged rats via the toll-like receptor 4 signaling pathway.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.15-23
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• 2003

Objective : The role of high frequency 120 Hz electroacupuncture(EA) in carrageenan-induced pain was studied by examining the alnalgesic effects, and prostaglandin $E_2(PGE_2)$ levels measurement and spinal N-methyl-D-aspartate(NMDA) receptor expression. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw. Method : Bilateral EA stimulation with 120 Hz were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles for a total of 30 min duration in carrageenan-injected rats. Results : EA stimulation showed significant analgesic effects as measured by analgesy-meter at all time points tested compared with controls. Three hours after carrageenan injection, PGE2 levels were measured by commercial kit. EA significantly inhibited PGE2 production in the right paw. The number of NR1 and NR2A, NMDA receptor, immunoreactive neurons was significantly increased in the superficial dorsal horn(laminae I-II) and nucleus proprius(laminae III-IV) of ipsilateral spinal cord at L4-5. But the number of carrageenan-induced NR1 and NR2A immunoreactive neuron, especially NR1 immunoreaction in the superficial dorsal horn, was reduced by 120 Hz EA stimulation. Conclusions : These results indicate that NMDA receptors may mediate transmission of nociceptive information originating in tissue inflammation of hind paw and high frequency 120 Hz EA stimulation have an alleviating action against local inflammatory pain.

• Biomedical Science Letters
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• v.13 no.2
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• pp.119-125
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• 2007

It is widely known that protein tyrosine kinases (PTKs) are involved in controlling many biological processes such as cell growth, differentiation, proliferation, survival and apoptosis. An $\alpha3\beta4$ subunit combination acts as a major functional acetylcholine receptor (nAChRs) in male rat major pelvic ganglion (MPG) neurons, and their activation induces fast inward currents and intracellular calcium increases. Recently it has been reported that the activity of acetylcholine receptors (AChRs) in some neurons can be negatively regulated by PTKs. However, the exact mechanism of regulation of nAChRs by PTKs is poorly understood. Therefore, we examined the potential role particular in nAChR by PTK using electrophysiology and calcium imaging in male rat MPG neurons. ACh induced inward currents and $(Ca^{2+})_i$ increases in MPG neurons, concomitantly. These responses were inhibited by more than 90% in $Na^+$- or $Ca^{2+}$- free solution. $\alpha$-conotoxin AuIB, a selective $\alpha3\beta4$ nAChR blocket, inhibited ACh-induced inward currents. Genistein (10 $\mu$M), a broad-spectrum tyrosine kinase inhibitor, markedly decreased ACh-induced currents and $Ca^{2+}$ transients, whereas 10 $\mu$M genistin, an inactive analogue, had little effect. Overall these data suggest that the activities of $\alpha3\beta4$ AChRs in MPG neurons are positively regulated by PTK. In conclusion, trosine kinase may be one of the key factors in the regulation of $\alpha3\beta4$ nAChRs in rat MPG neurons, which may play an important roles in the autonomic neuronal function such as synaptic transmission, autonomic reflex, and neuronal plasticity.