• Korean Journal of Veterinary Research
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• v.31 no.3
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• pp.253-258
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• 1991

The aims of this study were to investigate the effect of adenosine triphosphate (ATP), which has been known as the neurotransmitter of nonadrenergic, noncholinergic nerves, and the source of $Ca^{\sharp}$ in the effect of ATP on the isolated renal artery of pig. The results of this study were summarized as follows: 1. ATP caused the contraction and the contractile responses were increased in a dose-dependent manner between the concentration of ATP $2{\times}10^{-3}M$ and $10^{-2}M$ on the isolated renal artery of pig. 2. The contractile responses induced by ATP $(5{\times}10^{-3}M)$ were not blocked by pretreatment with cholinergic receptor blocker (atropine, $10^{-6}M$), $\alpha$-adrenergic recptor blocker(phentolamine, $10^{-6}M$) or $\beta$-adrenergic receptor blocker (propranolol, $10^{-6}M$), and $H_1$-receptor blocker (pyrilamine, $10^{-6}M$) or $H_2$-receptor blocker (cimetidine, $10^{-6}M$) on the isolated renal artery of pig. 3. The contractile responses induced by ATP $(5{\times}10^{-3}M)$ were not appeared in $Ca^{\sharp}$-free medium. As the concentration of $Ca^{\sharp}$ in $Ca^{\sharp}$-free medium was increased, the contractile responses induced by ATP $(5{\times}10^{-3}M)$ were enhanced but were completely inhibited by pretreatment with $Ca^{\sharp}$-channel blocker, papaverine $(5{\times}10^{-5}M)$ or verapamil $(5{\times}10^{-5}M)$ on the isolated renal artery of pig.

• Journal of Animal Science and Technology
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• v.51 no.4
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• pp.289-294
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• 2009

Inositol 1,4,5-triphosphate receptor type 1 (IP3R1) is a $Ca^{2+}$ release channel that responds to the second messenger IP3 and that modulates diverse cellular functions such as contraction/excitation, secretion, gene expression and cellular growth. We discovered single nucleotide polymorphisms (SNPs) within IP3R1 gene and analyzed associations between gene polymorphisms and carcass traits in Korean cattle (Hanwoo) in order to develop novel DNA markers at genomic level. Three SNPs were detected at the position of g.1428617A>G, g.1418843C>T and g.1414377C>T with 24 unrelated Hanwoo samples by direct sequencing of the PCR products. We found that genotype of g.1414377C>T SNP was associated with live weight (P<0.05) and carcass weight (P<0.01) using the general linear model of SAS package. These results suggest that polymorphism of IP3R1 gene was associated with weight-related traits in Hanwoo.

• Genomics & Informatics
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• v.5 no.2
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• pp.77-82
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• 2007

Serotonin (5-HT), the endogenous nonselective 5-HT receptor agonist, activates the inositol-1,4,5-triphosphate/calcium $(InsP3/Ca^{2+})$ signaling pathway and exerts both stimulatory and inhibitory actions on cAMP production and neuromodulin secretion in rat hypothalamic neurons. Specific mRNA transcripts for 5-HT1A, 5-HT2C and 5-HT4 were identified in rat hypothalamic neurons. These experiments were supported by combined techniques such as cAMP and a $Ca^{2+}$ assays in order to elucidate the associated receptors and signaling pathways. The cAMP production and neuromodulin release were profoundly inhibited during the activation of the Gi-coupled 5-HT1A receptor. Treatment with a selective agonist to activate the Gq-coupled 5-HT2C receptor stimulated InsP3 production and caused $Ca^{2+}$ release from the sarcoplasmic reticulum. Selective activation of the Gs-coupled 5-HT4 receptor also stimulated cAMP production, and caused an increase in neuromodulin secretion. These findings demonstrate the ability of 5-HT receptor subtypes expressed in neurons to induce neuromodulin production. This leads to the activation of single or multiple G-proteins which regulate the $InsP3/Ca^{2+}/PLC-{\gamma}$ and adenyl cyclase / cAMP signaling pathways.

• The Korean Journal of Physiology
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• v.22 no.1
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• pp.31-39
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• 1988

This study was carried out to investigate the action of adenosine triphosphate (ATP) on the motility of immature pig uterine smooth muscle. ATP appeared contractile responses in a dose-dependent manner, showing the maximal contraction at the concentration of $10^{-3}M$ in the uterine smooth muscle strip. The contractile responses by $ATP(10^{-4}M)$ were not affected by atropine $(10^{-6}M)$, phentolamine $(10^{-6}M)$, propranolol $(10^{-6}M)$, pyrilamine $(10^{-6}M)$, cimetidine $(10^{-6}M)$, and theophyulline $(5{\times}10^{-5}M)$, but were inhibited uncompetitively by quinidine. The effects of these drugs on the contractile responses by prostaglandin $F_{2{\alpha}}(PGF_{2{\alpha}})$ were also comparable to those observed with ATP. When muscle strips were pretreated with indomethacin $(5{\times}10^{-5}M)$ for 20 min., the contractile responses by $ATP(10^{-4}M)$ were completely inhibited. But the contractile responses by $PGF_{2{\alpha}}$ were not affected by indomethacin. These results suggest that ATP elicited the contraction through noncholinergic- and nonadrenergic-receptor mediated by prostaglandin $F_{2{\alpha}}$ in pig uterine smooth muscle.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.425-431
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• 2019

Platelet activation is essential for hemostatic process on blood vessel damage. However, excessive platelet activation can cause some cardiovascular diseases including atherosclerosis, thrombosis, and myocardial infarction. Scoparone is commonly encountered in the roots of genus Artemisia or Scopolia, and has been studied for its potential pharmacological properties including immunosuppression and vasorelaxation, but antiplatelet effects of scoparone have not been reported yet. We investigated the effect of scoparone on human platelet activation prompted by an analogue of thromboxane A₂, U46619. As the results, scoparone dose-dependently increased cyclic adenosine monophosphate (cAMP) levels as well as cyclic guanosine monophosphate (cGMP) levels, both being aggregation-inhibiting molecules. In addition, scoparone strongly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), substrates of cAMP dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by scoparone resulted in inhibition of Ca²⁺ mobilization in calcium channels in a dense tubular system, and phosphorylation of VASP by scoparone led to an inability of fibrinogen being able to bind to αIIb/β3. Finally, scoparone inhibited thrombin-induced fibrin clotting, thereby reducing thrombus formation. Therefore, we suggest that scoparone has a strong antiplatelet effect and is highly probable to prevent platelet-derived vascular disease.

• Journal of Applied Biological Chemistry
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• v.63 no.3
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• pp.235-241
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• 2020

An essential component of the hemostatic process during vascular damage is platelet activation. However, many cardiovascular diseases, such as atherosclerosis, thrombosis, and myocardial infarction, can develop due to excessive platelet activation. Isoscopoletin, found primarily in plant roots of the genus Artemisia or Scopolia, has been studied to demonstrate potential pharmacological effects on Alzheimer's disease and anticancer, but its mechanisms and role in relation to thrombus formation and platelet aggregation have not yet been discovered. This research investigated the effect of isoscopoletin on collagen-induced human platelet activation. As a result, isoscopoletin strongly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in a concentration-dependent manner. In addition, isoscopoletin greatly phosphorylated inositol 1,4,5-triphosphate receptor (IP₃R) and vasodilator-stimulated phosphoprotein (VASP), known substrates of cAMP-dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by isoscopoletin induced Ca²⁺ inhibition from the dense tubular system Ca²⁺ channels, and VASP phosphorylation was involved in fibrinogen binding inhibition by inactivating αIIb/β₃ in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clot production and finally reduced thrombus formation. Therefore, this research suggests that isoscopoletin has strong antiplatelet effects and is likely to be helpful for thrombotic diseases involving platelets by acting as a prophylactic and therapeutic agent.

• Korean Journal of Pharmacognosy
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• v.52 no.1
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• pp.26-33
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• 2021

During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.

• Development and Reproduction
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• v.23 no.1
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• pp.1-9
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• 2019

The ability of oocytes to undergo normal fertilization and embryo development is acquired during oocyte maturation which is transition from the germinal vesicle stage (GV), germinal vesicle breakdown (GVBD) to metaphase of meiosis II (MII). Part of this process includes redistribution of inositol 1, 4, 5-triphosphate receptor (IP3R), a predominant $Ca^{2+}$ channel on the endoplasmic reticulum membrane. Type 1 IP3R (IP3R1) is expressed in mouse oocytes dominantly. At GV stage, IP3R1 are arranged as a network throughout the cytoplasm with minute accumulation around the nucleus. At MII stage, IP3R1 diffuses to the entire cytoplasm in a more reticular manner, and obvious clusters of IP3R1 are observed at the cortex of the egg. This structural reorganization provides acquisition of $[Ca^{2+}]_i$ oscillatory activity during fertilization. In this review, general properties of IP3R1 in somatic cells and mammalian oocyte are introduced.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.5
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• pp.311-316
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• 2010

It is well-known that electrical field stimulation (EFS)-induced contraction is mediated by a cholinergic mechanism and other neurotransmitters. NO, ATP, calcitonin gene-related peptide (CGRP), and substance P are released by EFS. To investigate the purinergic mechanism involved in the EFS-induced contraction, purinegic receptors antagonists were used. Suramine, a non-selective P2 receptor antagonist, reduced the contraction induced by EFS. NF023 ($10^{-7}{\sim}10^{-4}M$), a selective P2X antagonist, inhibited the contraction evoked by EFS. Reactive blue ($10^{-6}{\sim}10^{-4}M$), selective P2Y antagonist, also blocked the contraction in a dose-dependent manner. In addition, P2X agonist ${\alpha}$,${\beta}$-methylene 5'-adenosine triphosphate (${\alpha}{\beta}MeATP$, $10^{-7}{\sim}10^{-5}M$) potentiated EFS-induced contraction in a dose-dependent manner. P2Y agonist adenosine 5'-[${\beta}$-thio]diphosphate trilithium salt ($ADP{\beta}S$, $10^{-7}{\sim}10^{-5}M$) also potentiated EFS-induced contractions in a dose-dependent manner. Ecto-ATPase activator apyrase (5 and 10 U/ml) reduced EFS-induced contractions. Inversely, 6-N,$N$-diethyl-D-${\beta}$,${\gamma}$- dibromomethylene 5'-triphosphate triammonium (ARL 67156, $10^{-4}M$) increased EFS-induced contraction. These data suggest that endogenous ATP plays a role in EFS-induced contractions which are mediated through both P2X-receptors and P2Y-receptors stimulation in cat esophageal smooth muscle.

• Korean Journal of Veterinary Service
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• v.19 no.2
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• pp.154-162
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• 1996

The effcets of adenosine 5'-triphosphate(ATP) were investigated on the uterine smooth muscle motility in the pig. The results were summarized as follows: 1. The effects of the porcine uterine smooth muscle and the contractile responses increased between the concentration of ATP $10^{-5}$ and $10^{-3}$ M with a dose-dependent manner. 2. The contractile response induced by ATP($10^{-4}$ M) was not blocked by pretreatment with cholinergic receptor blocker, atropine ($10^{-6}$ M) 3. The contractile response induced by ATP ($10^{-4}$ M) was not blocked by pretreatment with $\alpha$ -adrenergic receptor blocker, phentolamine(10$^{-6}$ M) and ${\beta}$-adrenergic blocker, propranolol ($10^{-6}$ M). 4. The contractile response induced by ATP($10^{-4}$ M) was not appeared in 4Ca^{++}$ -free medium. As the concentration of $Ca^{++}$ in $Ca^{++}$ -free medium was increased, the contractile response induced by ATP ($10^{-4}$ M) was enhenced but was completely inhibited by pretreatment with $Ca^{++}$ -channel blocker, papaverine($10^{-6}$ M) or verapamil($10^{-6}$ M). From these results, it was conclued that the effects of ATP were the contraction mediated by purinergic receptor in uterine smooth muscle of pig.