• Archives of Pharmacal Research
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• v.21 no.3
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• pp.315-319
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• 1998

Gastric smooth muscle of cats was used to investigate the involvement of protein kinase in vanadate-induced contraction. Vanadate caused a contraction of cat gastric smooth muscle in a dose-dependent manner. Vanadate-induced contraction was totally inhibited by 2 mM EGTA and 1.5 mM $LACI_3$ and significantly inhibited by $10\mu$M verapamil and $1\mu$M nifedipine, suggesting that vanadate-induced contraction is dependent on the extracellular $Ca^{2+}$ concentration, and the influx of extracellular $Ca^{2+}$ was mediated through voltage-dependent $Ca^{2+}$ channel. Both protein kinase C inhibitor and tyrosine kinase inhibitor significantly inhibited the vanadate-induced contraction and the combined inhibitory effect of two protein kinase inhibitors was greater than that of each one. But calmodulin antagonists did not have any influence on the vanadate-induced contraction. On the other hand, both forskolin ($1\mu$M) and sodium nitroprusside ($1\mu$M) significantly inhibited vanadate-induced contraction. Therefore, these results suggest that both protein kinase C and tyrosino kinase are involved in the vanadate-induced contraction which required the influx of extracellular $Ca^{2+}$ in cat gastric smooth muscle, and that the contractile mechanism of vanadate may be different from that of agonist binding to its specific receptor.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.463-469
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• 2022

Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A₂ generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca²⁺ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser¹⁷⁵⁶), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A₂ generation and associated signaling molecules, including cytosolic phospholipase A₂ and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β₃) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• The Korean Journal of Physiology
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• v.13 no.1_2
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• pp.41-50
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• 1979

The activation mechanism of K-induced contracture was studied in renal vascular muscle which does not generate an action potential readily and in taenia coli which generates a spike potential spontaneously. Helical strips of arterial muscle from rabbit renal arteries and longitudinal strips of taenia coli from guinea-pig's colons, respectively, were prepared. All experiments were performed in Tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept $35^{\circ}C$. Renal arterial muscles developed the contracture rapidly, which was composed of a small phasic and a large tonic components, when exposed to a 40 mM K-Tyrode solution. In the absence of external $Ca^{++}$, however, no K-contracture appeared. The contracture induced by K-depolarization was abolished by the treatment with verapamil, which is known to be a selective $Ca^{++}-blocker$ through potential-sensitive $Ca^{++}-channel$. K-contracture of taenia coli showed the contracture composed of a large phasic and a small tonic components. In the $Ca^{++}-free$ Tyrode solution, only the tonic component was abolished and almost no change in the phasic component was observed. The amplitude of tonic component was dependent on the external $Ca^{++}$; The tonic component increased dose-dependently by a stepwise increase of the external $Ca^{++}$, and this component decreased in parallel with the increase of verapamil in the external medium. The results of this experiment suggest that K-contracture of rabbit renal artery is the direct result of the influx of the external $Ca^{++}$, while that of taenia coli is the result of both $Ca^{++}$ influx and the release of sequestered $Ca^{++}$.

• Biomedical Science Letters
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• v.24 no.3
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• pp.253-262
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• 2018

Platelets are activated at sites of vascular injury via several molecules, such as adenosine diphosphate, collagen and thrombin. Full platelet aggregation is absolutely essential for normal hemostasis. Moreover, this physiological event can trigger circulatory disorders, such as thrombosis, atherosclerosis, and cardiovascular disease. Therefore, platelet function inhibition is a promising approach in preventing platelet-mediated circulatory disease. Many studies reported the involvement of mitogen-activated protein kinases (MAPKs) signaling pathways in platelet functions. However, these studies were limited. Thus, we examined MAPK signaling pathways in human platelets using specific MAPK inhibitors, such as PD98059, SB203580, and SP600125. We observed that these inhibitors were involved in calcium mobilization and influx in human platelets. They also suppressed thrombin-induced ${\alpha}$- and ${\delta}$-granule release. These results suggest that PD98059, SB203580, and SP600125 exhibit $Ca^{2+}$ antagonistic effects.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.97.2-97.2
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• 2003

(1R,9S)-(${\beta}$)-Hydrastine (HS) at 10-50 ${\mu}$M has been proven to have an inhibitory effect on dopamine biosynthesis in PC12 cells by the inhibition of tyrosine hydroxylase (TH) activity and TH gene expression. In the present study, therefore, the effects of HS on the basal and K$\^$+/-induced dopamine release, and Ca$\^$2+/ influx induced by high K$\^$+/ and caffeine in PC12 cells were investigated. The dopamine release by high K$\^$+/ (56 mM) was inhibited by co-incubation of 20 ${\mu}$M HS. Application of HS also significantly reduced the magnitude of the maintained Ca$\^$2+/ influx induced by K$\^$+/ depolarization. (omitted)

• Journal of Ginseng Research
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• v.47 no.6
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• pp.755-765
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• 2023

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca²⁺ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca²⁺ ([Ca²⁺]_i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca²⁺]_i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca²⁺]_i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca²⁺]_i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca²⁺ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca²⁺]_i.

• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.39-39
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• 2002

Microglia are known to have an important function as brain macrophage during immunological processes, oncogenesis, and regeneration in the central nervous system (CNS). A wide variety of ion channels have been identified and characterized in microglia including inward rectifier $K^{＋}$ channel (Kir), voltage dependent $K^{＋}$ channel (Kv), $Ca^{2＋}$-release activated $Ca^{2＋}$ channel (CRAC).(omitted)

• The Zoological Society Korea : Newsletter
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• v.12 no.2
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• pp.109.1-109
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• 1995

No Abstract, See Full Text

• Proceedings of the Zoological Society Korea Conference
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• 1995.10b
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• pp.245.1-245
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• 1995

No Abstract, See Full Text

• Molecules and Cells
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• v.21 no.3
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• pp.418-427
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• 2006

Ionotropic glutamate receptors (iGluRs) are ligand-gated nonselective cation channels that mediate fast excitatory neurotransmission. Although homologues of the iGluRs have been identified in higher plants, their roles are largely unknown. In this work we isolated a full-length cDNA clone (RsGluR) encoding a putative glutamate receptor from small radish. An RsGluR:mGFP fusion protein was localized to the plasma membrane. In Arabidopsis thaliana overexpressing the fulllength cDNA, glutamate treatment triggered greater $Ca^{2+}$ influx in the root cells of transgenic seedlings than in those of the wild type. Transgenic plants exhibited multiple morphological changes such as necrosis at their tips and the margins of developing leaves, dwarf stature with multiple secondary inflorescences, and retarded growth, as previously observed in transgenic Arabidopsis overexpressing AtGluR3.2 [Kim et al. (2001)]. Microarray analysis showed that jasmonic acid (JA)-responsive genes including defensins and JA-biosynthetic genes were up-regulated. RsGluR overexpression also inhibited growth of a necrotic fungal pathogen Botrytis cinerea possibly due to up-regulation of the defensins. Based on these results, we suggest that RsGluR is a glutamate-gated $Ca^{2+}$ channel located in the plasma membrane of higher plants and plays a direct or indirect role in defense against pathogen infection by triggering JA biosynthesis.