• Genomics & Informatics
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• v.10 no.2
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• pp.128-132
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• 2012

To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.41-46
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• 2014

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (${\alpha}$-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with ${\alpha}$-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, ${\alpha}$-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.547-554
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• 2018

Itching is a common clinical symptom of skin disease that significantly affects a patient's quality of life. Transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes and peripheral nerve fibers in skin are involved in the regulation of itching as well as pain. In this study, we investigated whether curcumin, which acts on TRPV1 receptors, affects histamine-induced itching in mice, using behavioral tests and electrophysiological approaches. We found that histamine-induced itching was blocked by topical application of curcumin in a concentration-dependent manner. In ex-vivo recordings, histamine-induced discharges of peripheral nerves were reduced by the application of curcumin, indicating that curcumin acts directly on peripheral nerves. Additionally, curcumin blocked the histamine-induced inward current via activation of TRPV1 (curcumin $IC_{50}=523nM$). However, it did not alter chloroquine-induced itching behavior in mice, which is associated with transient receptor potential ankyrin 1 (TRPA1). Taken together, our results suggest that histamine-induced itching can be blocked by topical application of curcumin through the inhibitory action of curcumin on TRPV1 receptors in peripheral nerves.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.192-198
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• 1995

The affinity of mequitazine, a non-sedating antihistamine, for muscarinic receptors was evaluated in the guinea-pig ventricle and ileum by in vitro binding techniques and functional studies. In binding studies, [$^3$H]quinuclidinyl benzilate (QNB) identified a single class of muscarinic receptors with similar apparent $K_{D}$ value of about 100 pM in two tissues. Mequitazine inhibited [$^3$H]QNB binding to muscarinic receptors competitively. Analysis of the mequitazine inhibition curve of [$^3$H]QNB binding to ventricular microsome and ileal homogenate indicated the presence of a single homogeneous binding site with Ki value of 25 nM and 18 nM, respectively. In functional studies, mequitazine caused parallel rightward shifts of concentration-response curves for carbachol and histamine in the isolated guinea-pig ileum. The slope values obtained from Schild plot analysis for the antagonistic action of mequitazine on muscarinic and histamine $H_1$-receptors were not significantly different from unity. The p $A_2$values of mequitazine for muscarinic and histamine $H_1$-receptors were about 7.6 ( $K_{M}$= 25.1 nM) and 8.88 ( $K_{H}$= 1.32 nM), respectively. These results indicate that the muscarinic receptor blocking action of mequitazine is 15 times less potent than the $H_1$receptor blocking action, but high concentration of this drug may cause the peripheral muscarinic receptor blocking effect.t.t.t.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.43-55
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• 1993

The present study was conducted to examine the characteristics of histamine on catecholamine secretion in the isolated perfused rat adrenal gland and to clarify the mechanism of its secretory action. Histamine (37.5 to 150 ug) injected into an adrenal vein evoked a dose-dependent significant secretory response of catecholamines (CA) from the rat adrenal gland. However, upon the repeated injection of histamine (150 ug) at 120 min intervals, CA secretion was rapidly decreased after third injection of histamine. Tachyphylaxis to releasing effects of CA evoked by histamine was observed by the repeated administration. The histamine-induced CA secretion was markedly inhibited by the pretreatment with chlorisondamine, diphenhydramine, ranitidine, $Ca^{++}-free$ Krebs solution, nicardipine and TMB-8 while was not affected by pirenzepine. Moreover, the CA secretion evoked by ACh was considerably reduced by the prior perfusion of histamine $(6.8{\times}10^{-5} M)$ for 30 min. These experimental data suggest that histamine causes secretion of CA in a calcium dependent manner from the perfused rat adrenal gland and that its secretory effect is mediated through activation of both $H_1-$ and $H_2-histaminergic$ receptors located in adrenal medulla, which may be associated with stimulation of cholinergic nicotinic receptors.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.192.1-192.1
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• 2003

Histamine is found in most tissues of the body and activates polymodal nociceptors via unmyelinated afferent C-fibres. We have demonstrated that bradykinin. acting at B2 bradykinin receptors. excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid in dorsal root ganglion. Histamine is known to the activator of phospholipase A2- arachidonic acid pathway via a G-protein- coupled H1 receptor. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.413-420
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• 2015

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing ${\alpha}2$ adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce $Ca^{2+}$ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger $Ca^{2+}$ peak or increase in the presence or absence of external $Ca^{2+}$. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced $[Ca^{2+}]_i$ signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

• Journal of Life Science
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• v.27 no.5
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• pp.600-610
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• 2017

It was common that the classification of itching was classified into four categories according to the neurophysiological mechanisms of pruritoceptive itching, neuropathic itching, neurogenic itching and psychogenic itching. Recently it was classified by clinical criteria. The neurotransmission pathway of itch is divided into histamine-dependent pathway and histamine-independent pathway. Different receptors and neuropeptides act on each itch mediator. Itch mediators such as histamine, BAM8-22, and chloroquine are transmitted through the histamine-dependent pathway. Cowhage spicule, protease, and TSLP (Thymic stromal lymphopoietin) have been reported to be related to the histamine-independent pathway. These itch mediators, receptors, and neuropeptides are the targets of treatment for itching. Although itching and pain are typical noxious stimuli, and in the past, it was argued that two senses were transmitted through one noxious stimulus receptor. It has recently been shown that itching and pain have an independent neurotransmitter system and both neuronal systems inhibit each other. In addition, the mutual antagonism between itching and pain is explained by various mechanisms. Recently, many new mediators and receptors are being studied. The studies on histamine 4 receptor (H4 receptor) have been actively conducted. And the H4 receptors are expressed in immune cells such as T cells. The therapeutic agent for blocking the H4 receptor can inhibit the inflammatory reaction itself, which is important for the itching and chronicization. Understanding the underlying mechanisms of itching and studying new itch mediators will lead to the development of effective therapies, and this is what I think the itching study will go on.

• Korean Journal of Veterinary Research
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• v.24 no.1
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• pp.17-23
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• 1984

To validate the physiological properties of the histamine receptors of ileal smooth muscle in dog, the effects of adrenergic-, cholineric-, and H-receptor antagonists on the responses of ileal smooth muscle strips to histamine were investigated. The results were summarized as follows; 1. Histamine caused the contraction of ileal smooth muscle and the contractile responses were increased between the concentration of histamine $10^{-7}M$ and $10^{-5}M$ with dose-dependent manner in dog. 2. The shorter the treatment interval of histamine, the lower the contractile activity until the treatment interval extended to 40 minutes. 3. The contractile response induced by histamine was completely blocked by the pre treatment with a $H_1$-receptor blocker, chlorpheniramine and not by the pretreatment with a $H_2$-receptor blockers cimetidine. 4. The contractile response induced by histamine was not blocked by the pretreatment with a cholinergic receptor blocker, atropine. 5. The contractile response induced by histamine was not blocked by the pretreatment with an ${\alpha}$-adrenergic receptor blocker, phenoxybenzamine, or a ${\beta}$-adrenergic receptor blocker, propranolol. From these results, it was suggested that the contraction induced by histamine was elicited through $H_1$-receptor on the ileal smooth muscle in dog.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.149-156
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• 2013

Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intestinal ICCs have not been previously investigated, and thus, in the present study, we investigated the effects of histamine on mouse small intestinal ICCs, and sought to identify the receptors involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials (in current clamp mode) from cultured ICCs. Histamine was found to depolarize resting membrane potentials concentration dependently, and whereas 2-PEA (a selective H1 receptor agonist) induced membrane depolarizations, Dimaprit (a selective H2-agonist), R-alpha-methylhistamine (R-alpha-MeHa; a selective H3-agonist), and 4-methylhistamine (4-MH; a selective H4-agonist) did not. Pretreatment with $Ca^{2+}$-free solution or thapsigargin (a $Ca^{2+}$-ATPase inhibitor in endoplasmic reticulum) abolished the generation of pacemaker potentials and suppressed histamine-induced membrane depolarization. Furthermore, treatments with U-73122 (a phospholipase C inhibitor) or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI; a phospholipase D inhibitor) blocked histamine-induced membrane depolarizations in ICCs. On the other hand, KT5720 (a protein kinase A inhibitor) did not block histamine-induced membrane depolarization. These results suggest that histamine modulates pacemaker potentials through H1 receptor-mediated pathways via external $Ca^{2+}$ influx and $Ca^{2+}$ release from internal stores in a PLC and PLD dependent manner.