• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.45-45
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• 2002

Extracellular ATP regulates a wide range of cellular function including the growth of prostate gland. Purinoceptors (ATP receptors) are divided into P2X (ligand-gated ion channels) and P2Y (G-protein-coupled receptor) subfamilies. In the present study, we investigated the types of purinoceptors in rat prostate neuroendocrine (RPNE) cells using whole-cell patch clamp technique, intracellular $Ca^{2+}$ measurement and RT-PCR analysis.(omitted)d)

• Molecules and Cells
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• v.37 no.3
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• pp.196-201
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• 2014

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by the vascular remodeling of the pulmonary arterioles, including formation of plexiform and concentric lesions comprised of proliferative vascular cells. Clinically, PAH leads to increased pulmonary arterial pressure and subsequent right ventricular failure. Existing therapies have improved the outcome but mortality still remains exceedingly high. There is emerging evidence that the seven-transmembrane G-protein coupled receptor APJ and its cognate endogenous ligand apelin are important in the maintenance of pulmonary vascular homeostasis through the targeting of critical mediators, such as Kr$\ddot{u}$ppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and microRNAs (miRNAs). Disruption of this pathway plays a major part in the pathogenesis of PAH. Given its role in the maintenance of pulmonary vascular homeostasis, the apelin-APJ pathway is a potential target for PAH therapy. This review highlights the current state in the understanding of the apelin-APJ axis related to PAH and discusses the therapeutic potential of this signaling pathway as a novel paradigm of PAH therapy.

• Food Science and Industry
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• v.50 no.4
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• pp.12-23
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• 2017

Gustation, initiated by the detection of taste molecules by specific receptors expressed in taste cells, plays an essential role in food selection and consequently in overall nutrition for humans. In the past decade, a remarkable amount of knowledge of taste perception in the neurology, molecular biology, and genetics has emerged, particularly in basic tastes- sweet, bitter, sour, salt and umami. Among them, sweet, bitter and umami are recognized via the specific G-protein coupled receptors. Salt and sour are primarily mediated by apically located ion channel-type receptors. Because excessive salt or sugar consumption leads to high rates of diet-associated diseases and it comes from eating prepared or processed foods, an understanding of the underlying mechanisms in salt and sweet perception is crucial in food industry. This review will focus on recent progress of the perception of salt and sweet taste to provide basic knowledge for reducing salt and sugar consumption.

• 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)

• Molecules and Cells
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• v.25 no.1
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• pp.91-98
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• 2008

The Glu/$Asp^{7.32}$ residue in extracellular loop 3 of the mammalian type-I gonadotropin-releasing hormone receptor (GnRHR) interacts with $Arg^8$ of GnRH-I, conferring preferential ligand selectivity for GnRH-I over GnRH-II. Previously, we demonstrated that the residues (Ser and Pro) flanking Glu/$Asp^{7.32}$ also play a role in the differential agonist selectivity of mammalian and non-mammalian GnRHRs. In this study, we examined the differential antagonist selectivity of wild type and mutant GnRHRs in which the Ser and Pro residues were changed. Cetrorelix, a GnRH-I antagonist, and Trptorelix-2, a GnRH-II antagonist, exhibited high selectivity for mammalian type-I and non-mammalian GnRHRs, respectively. The inhibitory activities of the antagonists were dependent on agonist concentration and subtype. Rat GnRHR in which the Ser-Glu-Pro (SEP) motif was changed to Pro-Glu-Val (PEV) or Pro-Glu-Ser (PES) had increased sensitivity to Trptorelix-2 but decreased sensitivity to Cetrorelix. Mutant bullfrog GnRHR-1 with the SEP motif had the reverse antagonist selectivity, with reduced sensitivity to Trptorelix-2 but increased sensitivity to Cetrorelix. These findings indicate that the residues flanking $Glu^{7.32}$ are important for antagonist as well as agonist selectivity.

• Biomolecules & Therapeutics
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• v.28 no.6
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• pp.569-575
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• 2020

Crotamiton is an anti-scabies drug, but it was recently found that crotamiton also suppresses non-scabietic itching in mice. However, the underlying mechanism is largely unclear. Therefore, aim of the study is to investigate mechanisms of the anti-pruritic effect of crotamiton for non-scabietic itching. Histamine and chloroquine are used as non-scabietic pruritogens. The effect of crotamiton was identified using fluorometric intracellular calcium assays in HEK293T cells and primary cultured dorsal root ganglion (DRG) neurons. Further in vivo effect was evaluated by scratching behavior tests. Crotamiton strongly inhibited histamine-induced calcium influx in HEK293T cells, expressing both histamine receptor 1 (H1R) and transient receptor potential vanilloid 1 (TRPV1), as a model of histamine-induced itching. Similarly, it also blocked chloroquine-induced calcium influx in HEK293T cells, expressing both Mas-related G-protein-coupled receptor A3 (MRGPRA3) and transient receptor potential A1 (TRPA1), as a model of histamine-independent itching. Furthermore, crotamiton also suppressed both histamine- and chloroquine-induced calcium influx in primary cultures of mouse DRG. Additionally, crotamiton strongly suppressed histamine- and chloroquine-induced scratching in mice. Overall, it was found that crotamiton has an anti-pruritic effect against non-scabietic itching by histamine and chloroquine. Therefore, crotamiton may be used as a general anti-pruritic agent, irrespective of the presence of scabies.

• Biomedical Science Letters
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• v.15 no.4
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• pp.319-326
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• 2009

Extracellular ATP elicits diverse physiological effects by binding to the G-protein-coupled P2Y receptors on the plasma membrane. In addition to the short-term effects of extracellular nucleotides on cell functions, there is evidence that such purinergic signalling can have long-term effects on cell proliferation, differentiation and death. The 3T3-L1 cell line derived from mouse embryo is a well-established and commonly utilized in vitro model for adipocytes differentiation and function. However, the distributions and roles of P2Y subtypes are still unknown in the preadipocyte. In this study, we identified the distributions and roles of P2Y subtypes in preadipocyte using $Ca^{2+}$ imaging and realtime PCR. ATP increased the $[Ca^{2+}]_i$ in a concentration-dependent manner. ATP increased $Ca^{2+}$ in absence and/or presence of extracellular $Ca^{2+}$. Suramin, non-selective P2Y blocker, largely blocked the ATP-induced $Ca^{2+}$ response. U73122, a PLC inhibitor, completely inhibited $Ca^{2+}$ mobilization in 3T3-L1 cells. The mRNA expression by realtime PCR of P2Y subtypes was $P2Y_2:P2Y_5:P2Y_6=1.0:12.5:0.3$. In conclusion, we showed that $P2Y_5$ receptor is a dominant purinergic receptor in preadipocytes, and multiple P2Y receptors could involve in differentiation and migration via regulating of intracellular calcium concentration.

• Molecules and Cells
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• v.20 no.2
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• pp.263-270
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• 2005

Transactivation of EGF-receptor (EGFR) by G-protein coupled receptors (GPCRs) is emerging as an important pathway in cell proliferation, which plays a crucial role in the development of atherosclerotic lesion. Angiotensin II (Ang II) has been identified to have a major role in the formation of atherosclerotic lesions, although the underlying mechanisms remain largely unclear. We hypothesize that Ang II promotes the proliferation and migration of smooth muscle cells through the release of heparin-binding epidermal growth factor like growth factor (HB-EGF), transactivation of EGFR and activation of Akt and Erk 1/2, with matrix metalloproteases (MMPs) playing a dispensable role. Primary rat aortic smooth muscle cells were used in this study. Smooth muscle cells rendered quiescent by serum deprivation for 12 h were treated with Ang II (100 nM) in the presence of either GM6001 ($20{\mu}M$), a specific inhibitor of MMPs or AG1478 ($10{\mu}M$), an inhibitor of EGFR. The levels of phosphorylation of EGFR, Akt and Erk 1/2 were assessed in the cell lysates. Inhibition of MMPs by GM6001 significantly attenuated Ang II-stimulated phosphorylation of EGFR, suggesting that MMPs may be involved in the transactivation of EGFR by Ang II receptor. Furthermore Ang II-stimulated proliferation and migration of smooth muscle cells were significantly blunted by inhibiting MMPs and EGFR and applying HB-EGF neutralization antibody, indicating that MMPs, HB-EGF and EGFR activation is necessary for Ang-II stimulated migration and proliferation of smooth muscle cells. Our results suggest that inhibition of MMPs may represent one of the strategies to counter the mitogenic and motogenic effects of Ang II on smooth muscle cells and thereby prevent the formation and development of atherosclerotic lesions.

• Development and Reproduction
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• v.10 no.3
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• pp.159-168
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• 2006

Rodents and many other mammals have two chemosensory systems that mediate responses to pheromones, the main and accessory olfactory system, MOS and AOS, respectively. The chemosensory neurons associated with the MOS are located in the main olfactory epithelium, while those associated with the AOS are located in the vomeronasal organ(VNO). Pheromonal odorants access the lumen of the VNO via canals in the roof of the mouth, and are largely thought to be nonvolatile. The main pheromone receptor proteins consist of two superfamilies, V1Rs and V2Rs, that are structurally distinct and unrelated to the olfactory receptors expressed in the main olfactory epithelium. These two type of receptors are seven transmembrane domain G-protein coupled proteins(V1R with $G_{{\alpha}i2}$, V2R with $G_{0\;{\alpha}}$). V2Rs are co-expressed with nonclassical MHC Ib genes(M10 and other 8 M1 family proteins). Other important molecular component of VNO neuron is a TrpC2, a cation channel protein of transient receptor potential(TRP) family and thought to have a crucial role in signal transduction. There are four types of pheromones in mammalian chemical communication - primers, signalers, modulators and releasers. Responses to these chemosignals can vary substantially within and between individuals. This variability can stem from the modulating effects of steroid hormones and/or non-steroid factors such as neurotransmitters on olfactory processing. Such modulation frequently augments or facilitates the effects that prevailing social and environmental conditions have on the reproductive axis. The best example is the pregnancy block effect(Bruce effect), caused by testosterone-dependent major urinary proteins(MUPs) in male mouse urine. Intriguingly, mouse GnRH neurons receive pheromone signals from both odor and pheromone relays in the brain and may also receive common odor signals. Though it is quite controversial, recent studies reveal a complex interplay between reproduction and other functions in which GnRH neurons appear to integrate information from multiple sources and modulate a variety of brain functions.

• Journal of Korean Physical Therapy Science
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• v.11 no.1
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• pp.20-27
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• 2004

It is widely accepted that smooth muscle contraction is triggered by intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR) and from the extracellular space, The increased $[Ca^{2+}]_i$ can phosphorylate the 20-kDa myosin light chain ($MLC_{20}$) by activating MLC kinase (MLCK), and this initiates smooth muscle contraction. In addition to the $[Ca^{2+}]_i$-MLCK-tension pathway, a number of intracellular signal molecules, including mitogen-activated protein kinase (MAPK), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and Rho-associated coiled coil-forming protein kinase (ROCK), play important roles in the regulation of smooth muscle contraction. However, the mechanisms regulating contraction of caldesmon (CaD), actin-binding protein, are not entirely elucidated in the presence of $Ca^{2+}$. It is known that CaD tightly interacts with actin and inhibits actomyosin ATPase activity. Therefore, the purpose of the present study was to investigate the roles of $Ca^{2+}$-dependent CaD in smooth muscle contraction. Endothelin-1 (ET-1), G-protein coupled receptor agonist and vasoconstrictor, increased both vascular smooth contraction and phosphorylation of CaD in the presence of $Ca^{2+}$. These results suggest that ET-1 induces contraction and phosphorylation of CaD in rat aortic smooth muscle, which may he mediated by the increase of $[Ca^{2+}]_i$.