• Genomics & Informatics
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• 제10권2호
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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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• 제18권1호
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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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• 제22권5호
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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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• 제3권3호
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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.

• 대한약리학회지
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• 제29권1호
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• pp.43-55
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• 1993

흰쥐 관류부신에서 histamine의 catecholamine (CA) 분비작용의 특성과 기전을 규명코자 연구한 결과는 다음과 같다. Histamine $(37.5{\sim}150\;{\mu}g)$을 부신정맥내에 주사 하였을 때 현저한 용량 의존성의 CA 분비작용을 나타내었다. 그러나 histamine $(150\;{\mu}g)$을 120분 간격으로 반복 투여시 제 3차 투여시부터는 CA 분비효과가 뚜렷이 감소하였다. 즉, histamine의 반복투여로 인한 반응급강현상을 관찰할 수 있었다. Histamine의 CA 분비작용은 chlorisondamine, diphenhydrarmine, ranitidine, $Ca^{++}-free$ Krebs 용액의 관류, nicardipine 및 TMB-8 등의 전처치로 유의하게 억제 되었으나 pirenzepine의 전처치에 의해서는 별다른 영향을 받지 않았다. 더우기 histamine $(6.8{\times}10^{-5}M)$으로 30분간 관류시킨 후에 ACh $(50{\mu}g)$의 CA 분비작용이 상당히 억제됨을 나타내었다. 이상과 같은 연구 결과로 보아 histamine은 흰쥐 적출관류 부신에서 현저한 CA 분비작용을 나타내었으며 칼슘 의존성이었다. 이러한 CA 분비작용은 $H_1-$ 및 $H_2-$ 양수용체의 활성화를 통해서 일어나며 또한 부신의 nicotine 수용체와도 관련성이 있는 것으로 사료된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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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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• 제19권5호
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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.

• 생명과학회지
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• 제27권5호
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• pp.600-610
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• 2017

가려움증의 분류는 수용체성 가려움증(Pruritoceptive itch), 신경병증 가려움증(Neuropathic itch), 신경성 가려움증(Neurogenic itch), 심인성 가려움증(Psychogenic itch)의 신경생리학적 기전에 따른 4가지 카테고리로 분류하는 것이 일반적이었으나 최근 임상적인 기준을 통해 분류하기도 한다. 가려움증의 신경전달 경로는 히스타민-의존 경로와 히스타민-비의존 경로 2가지로 나뉘며 각 가려움증 매개체마다 서로 다른 수용체와 신경펩티드가 작용한다. 히스타민, BAM8-22, chloroquine 등의 가려움증 매개체는 히스타민-의존 경로를 통해 신호가 전달되며 cowhage spicule, 단백분해효소(protease), TSLP (Thymic stromal lymphopoietin) 등의 매개체가 히스타민-비의존 경로와 관련있다는 보고가 있다. 이러한 가려움증 매개체, 수용체, 신경펩티드는 가려움증 치료의 대상이 된다. 가려움증과 통증은 대표적인 유해자극으로서 과거에는 두 감각이 하나의 유해자극수용체를 통해 전달된다는 주장이 있었지만 최근 밝혀진 바에 따르면 가려움증과 통증은 독립적인 신경전달체계를 가지고 있으며 두 신경체계는 서로 억제작용을 한다. 가려움증 뉴런의 선택적 소집단이 존재한다는 주장을 뒷받침하는 연구들이 이 주장에 무게를 싣고 있다. 또한 가려움증과 통증의 상호 길항작용에 대해서도 다양한 기전으로 설명되고 있다. 최근에도 새롭게 연구되는 매개체와 수용체들이 많은 연구들을 통해 밝혀지고 있다. 특히 최근에는 히스타민 4 수용체에 대한 연구가 활발히 진행되고 있는데, 이는 T 세포 같은 면역세포 자체에 발현되어 있어 이 H4 수용체를 차단하는 치료제는 말초의 매개체를 차단하는 기존의 히스타민 수용체 차단제와는 달리 가려움증 만성화에 중요한 염증 반응 자체를 억제할 수 있다는 점에서 그 유용성이 크다고 할 수 있다. 가려움증의 기본적인 발생 기전에 대한 이해와 새로운 가려움증 매개체에 대한 연구는 효과적인 치료법의 개발로 이어질 것이며 이것이 가려움증 연구가 나아갈 바로 생각한다.

• 대한수의학회지
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• 제24권1호
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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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• 제17권2호
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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.