• YAKHAK HOEJI
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• v.34 no.3
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• pp.180-191
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• 1990

A comparison was made of the effects of selective ${\alpha_1}-adrenoceptor$ agonist phenylephrine and selective ${\alpha_2}-adrenoceptor$ agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at $EC_{50}$ level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at $EC_{50}$ level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor (EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the ${\alpha_1}-adrenoceptor$ antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of ${\alpha_1}-adrenoceptor$ with dibenamine.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.242-248
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• 1999

Diazepam, a benzodiazepine (BDZ) agonist, produces sedation and flumazenil, a BDZ antagonist, blocks these actions. The aim of this study was to examine the effects of BDZs on cortical electroencephalogram (EEG) in rats. The recording electrodes were implanted over the frontal and parietal cortices bilaterally, and the reference and ground electrodes over cerebellum under ketamine anesthesia. To assess the effects of diazepam and flumazenil, rats were injected with diazepam (1 mgHg, i.p.) and/or flumazenil ( 1 mg/kg, i.p.), and the EEG was recorded before and after drugs. Normal awake had theta peak in the spectrum and low amplitude waves, while normal sleep showed large amplitude of slow waves. The powers of delta, theta and alpha bands were increased during sleep compared with during awake. Diazepam reduced the mobility of the rat and induced sleep with intermittent fast spindles and large amplitude of slow activity, and it produced broad peak over betaL band and increased the power of gamma band, which were different from EEG patterns in normal sleep. Saline injection awakened rats and abolished fast spindles for a short period about 2-5 min from EEG pattern during diazepam-induced sleep. Flumazenil blocked both diazepam-induced sleep and decreased the slow activities of delta, theta, alpha and betaL, but not of gamma activity for about 10 min or more. This study may indicate that decrease in power of betaL and betaH bands can be used as the measure of central action of benzodiazepines, and that the EEG parameters of benzodiazepines have to be measured without control over the behavioral state by experimenter.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.52-52
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• 2003

Granulocyte-macrophage colony stimulating factor (GM-CSF) is synthesized in the female reproductive tract and has been shown to play an important role in human and murine embryo development and implantation. However, the mechanism of GM-CSF on the embryo development is unknown. Recent studies suggested that GM-CSF may be increase the expression of implantation relented genes, such as interleukin-1 (IL-1) system. Our aim of this study was to compare the interleukin-1$\alpha$ (IL-1$\alpha$), interleukin-1$\beta$ (IL-1$\beta$) and interleukin-1 receptor antagonist (IL-lra) mRNA between the GM-CSF supplemented group and control group in mouse embryos. Mouse 2-cell embryos were cultured in P-1 medium supplemented with or without mouse GM-CSF (10 ng/ml). The number of total and apoptotic cell in blastocyst were assessed by TUNEL. And then, the expression of IL-1$\alpha$, IL-1$\beta$ and IL-1ra mRNA in blastocyst were examined by RT-PCR.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.641-647
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• 2017

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-${\kappa}B$ activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, known to play an anti-inflammatory role. To investigate whether PPAR-${\gamma}$ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-${\gamma}$ antagonist before treatment of galangin. We found that PPAR-${\gamma}$ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-${\alpha}$ and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-${\kappa}B$, and PPAR-${\gamma}$ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

• International Journal of Oral Biology
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• v.36 no.2
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• pp.71-78
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• 2011

Using whole cell current- and voltage-clamp recording we investigated the characteristics and pharmacology of group I metabotropic glutamate receptor (mGluR)-mediated responses in rat medial vestibular nucleus (MVN) neurons. In current clamp conditions, activation of mGluR I by application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced a direct excitation of MVN neurons that is characterized by depolarization and increased spontaneous firing frequency. To identify which of mGluR subtypes are responsible for the various actions of DHPG in MVN, we used two subtype-selective antagonists. (S)-(+)- alpha-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist that is selective for mGluR5. In voltage clamp conditions, DHPG application increased the frequency of spontaneous and miniature inhibitory postsynaptic currents (IPSCs) but had no effect on amplitude distributions. Antagonism of the DHPG-induced increase of miniature IPSCs required the blockade of both mGluR1 and mGluR5. DHPG application induced an inward current, which can be enhanced under depolarized conditions. DHPG-induced current was blocked by LY367385, but not by MPEP. Both LY367385 and MPEP antagonized the DHPG-induced suppression of the calcium activated potassium current ($I_{AHP}$). These data suggest that mGluR1 and mGluR5 have similar roles in the regulation of the excitability of MVN neurons, and show a little distinct. Furthermore, mGluR I, via pre- and postsynaptic actions, have the potential to modulate the functions of the MVN.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.474-482
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• 1997

There have been some case reports of the coexistence of extraadrenal pheochromocytoma and renal artery stenosis. Some reporters proposed that their coexistence may be associated through a common pathophysiological mechanism mediated by catecholamine secretion. Also some noted that trasient renal artery stenosis due to a spasm was induced by the catecholamines released from pheochromacytoma. We report a case of left paraaortic extraadrenal pheochromacytoma that had a transient oral captopril test positive result. After 5 days ${\alpha}$-antagonist reduced the vasospastic response of catecholamines. After surgical removal of the tumor, plasma catecholamines and urinary vanillyhnandelic acid concentrations as well as the blood pressure level, were restored to normal.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.59-67
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• 1982

1) Oxymetazoline, which has been known as an agonist for${\alpha}_1-adrenoceptor$ in various peripheral tissues, caused a pressor response in urethane-anesthetized rabbits when given intra-ventricularly. This pressor response was little affected by pretreatment of rabbits with i.v. guanethidine or chlorisondamine, but it was weakened in rabbits pretreated with either of i.v. phentolamine or guanethidine and chlorisondamine and in guanethidine-pretreated adrenal-ligated rabbits. 2) The pressor to intraventricular oxymetazoline was markedly attenuated by intraventricular pretreatment with prazosin, whereas intraventricular pretreatment with yohimbine or piperoxan did not affect this response. 3) Reserpine-pretreated rabbits also responded with hypertension to intraventricular oxymetazoline, which was markedly diminished by pretreatment with intraventricular prazosin but not affected by yohimbine. 4) Oxymetazoline, given intravenously, produced a pressor response in both whole and spinal rabbits. Intravenous prazosin, phentolamine and yohimbine, in this order, showed greater antagonizing effect to this pressor response. 5) The results indicate that oxymetazoline acts an agonist for ${\alpha}_1-adrenoceptors$ in the rabbit brain participating in the regulation of the blood pressure and in the vasculature of rabbits.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.99-110
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• 1985

Majarine that was isolated from Berberis Koreasra Palibin (Berberidaceae) is the isoquinoline alkaloid. The effects of dopaminergic and serotonergic antagonists on majarine induced changes in body temperature were studied in the mouse. Intraperitoneal administration of majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine caused a slight increase in body temperature. Majarine-induced hyperthermia was attenuated by the 5-HT antagonist, cyproheptadine However, it caused hyothermia in mice pretreated with the DA antagonist, haloperidol, and hyperthermia in mice pretreated with haloperidol and cyproheptadine in comparision with haloperidol pretreatment. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol and cyproheptadine, respectively. In reserpine pretreated mice, majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine pretreated with haloperidol caused no significant effect in body temperature. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol pretreatment in mice treated with reserpine and ${\alpha}$-methyl-p-tyrosine. These data suppose that both dopaminergic and serotonergic mechanisms in the brain mediate the effects of majarine on body temperature. We propose that majarine directly stimulate DA receptor, which secondarilly activate 5-HT neurons to cause changes in body temperature.

• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.327-332
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• 2001

In recent years, experimental evidence have been suggested that melatonin has either contractive or relaxing effects on the vascular smooth muscle in vitro. But the effect of melatonin on the cardiovascular system in vivo had been emphasized about the hypotensive effect. In this work, we found not only hypotensive effect but also hypertensive effect of melatonin in rats and attempted to determine the mechanism of these effects elicited by melatonin. Regadless of concentration, melatonin(0.002~5 mg/kg) produced increase in mean blood pressure (MBP) in 36% (54/150 cases) and decrease in mean blood pressure in 64%(96/150 cases). As a whole melatonin caused an increase or a decrease in MBP without compensatory decrease or increase in heart rate. The melatonin-induced hypertension was abolished by the pretreatment of phenoxybenzamine, a ${\alpha}$-adrenoceptor antagoninst. The melatonin-induced hypotension was abolished by the pretreatment of propranolol, a ${\beta}$-adrenoceptor antagonist, ODQ, a NO-sensitive guanylate cyclase inhibitor, or nifedipine, a L-type $Ca^{2+}$ channel blocker, but not by bilateral cervical vagotomy. The results indicate that melatonin-induced hypertension may be related to ${\alpha}$-adrenoceptor stimulation and melatonin-indued hypotension may be related to ${\beta}$-adrenoceptor stimulation, inhibition of $Ca^{2+}$ channel and/or activation of guanylate cyclase.