No abstract available.
Animals ; Brain* ; Cats* ; Inositol 1,4,5-Trisphosphate* ; Inositol*

No abstract available.
Animals ; Cerebellum* ; Inositol 1,4,5-Trisphosphate* ; Inositol* ; Rats*

Previously, we reviewed biological evidence that mercury could induce autoimmunity and coronary arterial wall relaxation as observed in Kawasaki syndrome (KS) through its effects on calcium signaling, and that inositol 1,4,5-triphosphate 3-kinase C (ITPKC) susceptibility in KS would predispose patients to mercury by increasing Ca2+ release. Hg2+ sensitizes inositol 1,4,5-triphosphate (IP3) receptors at low doses, which release Ca2+ from intracellular stores in the sarcoplasmic reticulum, resulting in delayed, repetitive calcium influx. ITPKC prevents IP3 from triggering IP3 receptors to release calcium by converting IP3 to inositol 1,3,4,5-tetrakisphosphate. Defective IP3 phosphorylation resulting from reduced genetic expressions of ITPKC in KS would promote IP3, which increases Ca2+ release. Hg2+ increases catecholamine levels through the inhibition of S-adenosylmethionine and subsequently catechol-O-methyltransferase (COMT), while a single nucleotide polymorphism of the COMT gene (rs769224) was recently found to be significantly associated with the development of coronary artery lesions in KS. Accumulation of norepinephrine or epinephrine would potentiate Hg2+-induced calcium influx by increasing IP3 production and increasing the permeability of cardiac sarcolemma to Ca2+. Norepinephrine and epinephrine also promote the secretion of atrial natriuretic peptide, a potent vasodilator that suppresses the release of vasoconstrictors. Elevated catecholamine levels can induce hypertension and tachycardia, while increased arterial pressure and a rapid heart rate would promote arterial vasodilation and subsequent fatal thromboses, particularly in tandem. Genetic risk factors may explain why only a susceptible subset of children develops KS although mercury exposure from methylmercury in fish or thimerosal in pediatric vaccines is nearly ubiquitous. During the infantile acrodynia epidemic, only 1 in 500 children developed acrodynia whereas mercury exposure was very common due to the use of teething powders. This hypothesis mirrors the leading theory for KS in which a widespread infection only induces KS in susceptible children. Acrodynia can mimic the clinical picture of KS, leading to its inclusion in the differential diagnosis for KS. Catecholamine levels are often elevated in acrodynia and may also play a role in KS. We conclude that KS may be the acute febrile form of acrodynia.
Acrodynia ; Arterial Pressure ; Autoimmunity ; Calcium ; Calcium Signaling ; Catechol O-Methyltransferase ; Catecholamines ; Child ; Coronary Vessels ; Diagnosis, Differential ; Epinephrine ; Heart Rate ; Humans ; Hydrazines ; Hypertension ; Inositol ; Inositol 1,4,5-Trisphosphate ; Inositol 1,4,5-Trisphosphate Receptors ; Inositol Phosphates ; Mucocutaneous Lymph Node Syndrome ; Norepinephrine ; Permeability ; Phosphorylation ; Polymorphism, Single Nucleotide ; Powders ; Relaxation ; Risk Factors ; S-Adenosylmethionine ; Sarcolemma ; Sarcoplasmic Reticulum ; Tachycardia ; Thimerosal ; Thrombosis ; Tooth ; Tooth Eruption ; Vaccines ; Vasoconstrictor Agents ; Vasodilation

OBJECTIVE: We reported the overcoming effect of Ni2+ on the in vitro 2-cell block of mouse embryos. In this study, we aim to investigate whether Ni2+ should induce intracellular Ca2+ transient in the mouse embryos. MATERIALS AND METHODS: Embryos were collected at post hCG 32hr from the oviduct of the ICR mouse and cultured in M2 medium omitted phenol red. Intracellular Ca2+ was checked by using a confocal laser scanning microscope and fluo-3AM by using various intracellular Ca2+ antagonists. RESULTS: In 1mM Ni2+ treated medium which contained Ca2+(1.71mM), 75.7% of the embryos showed [Ca2+]i transient about 200 sec later. In the Ca2+-free medium, 69.8% of the embryos showed [Ca2+]i transient. In U73122, phospholipaseC(PLC) inhibitor (5uM, 10min) pretreated group, 33.3% of the embryos showed [Ca2+]i transient. Heparine, inositol 1,4,5-triphosphate receptor(IP3R) antagonist preinjected embryos showed no response with 1mM Ni2+. In danthrolene treatment, ryanodine receptor(RyR)-antagonist, 43% embryos showed [Ca2+]i transient but they showed delayed response about 340sec in the presence of Ca2+. CONCLUSIONS: Summing up the above results, Ni2+ seems to induce Ca2+-release from the Ca2+-store even in the Ca2+-free medium. IP3 receptors of the mouse 2-cell embryos might have an essential role for the intracellular Ca2+ increase by Ni2+.
Animals ; Embryonic Structures* ; Heparin ; Inositol 1,4,5-Trisphosphate ; Inositol 1,4,5-Trisphosphate Receptors ; Mice* ; Mice, Inbred ICR ; Oviducts ; Phenolsulfonphthalein ; Ryanodine

Inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is an important intracellular channel for releasing Ca²⁺. In order to investigate the effects of the ITPR1 overexpression on Ca²⁺ concentration and lipid content in duck uterine epithelial cells and its effects on calcium transport-related genes, the structural domain of ITPR1 gene of duck was cloned into an eukaryotic expression vector and transfected into duck uterine epithelial cells. The overexpression of the ITPR1 gene, the concentration of Ca²⁺, the lipid content, and the expression of other 6 calcium transport-related genes was determined. The results showed that the concentration of Ca²⁺ in uterine epithelial cells was significantly reduced after transfection (P<0.05), the triglyceride content was significantly increased (P<0.01), and the high-density lipoprotein content was significantly decreased (P<0.01). The correlation analysis results showed that the overexpression of the C-terminal half of the ITPR1 gene was significantly positively correlated with the total cholesterol content (P<0.01), which was significantly positively correlated with the low-density lipoprotein content (P<0.05). The overexpression of the N-terminal half of the ITPR1 gene was significantly positively correlated with the triglyceride content (P<0.01), which was significantly negatively correlated with the concentration of Ca²⁺ (P<0.05). RT-qPCR results of 6 calcium transport-related genes showed that the overexpression of the C-terminal half of the ITPR1 gene significantly inhibited the expression of the IP3R2, VDAC2 and CAV1 genes, and the overexpression of the N-terminal half of the ITPR1 gene significantly promoted the expression of the IP3R3 and CACNA2D1 genes. In conclusion, the ITPR1 gene overexpression can promote Ca²⁺ release in duck uterus epithelial cells, promote the synthesis of triglyceride, low-density lipoprotein and cholesterol, and inhibit the production of high-density lipoprotein, and the ITPR1 gene overexpression affected the expression of all 6 calcium transport-related genes.
Animals ; Calcium/metabolism* ; Ducks/genetics* ; Epithelial Cells ; Female ; Inositol ; Inositol 1,4,5-Trisphosphate Receptors ; Lipids ; Uterus

Background: Myo-inositol has emerged as one of the preventive therapies for the development of gestational diabetes mellitus in at-risk populations. This systematic review and meta-analysis was conducted to determine the efficacy and safety of myo-inositol in decreasing the incidence of gestational diabetes in overweight and obese pregnant women. Methodology: This meta-analysis was conducted using the standard Cochrane methodology and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. Inclusion criteria were randomized controlled trials (RCTs) that enrolled overweight and obese pregnant women and used myo-inositol supplementation. The primary outcome was the incidence of gestational diabetes mellitus at 24-28 weeks. Secondary outcomes included cesarean section rate, the incidence of pregnancy-induced hypertension, macrosomia and preterm delivery. Risk ratios (RRs) and 95% confidence intervals (CIs) were used for dichotomous data. Results: Six RCTs were included. Compared to standard micronutrient supplementation, standard dose of myo-inositol (4 g) may reduce the incidence of GDM (RR 0.54; CI [0.30, 0.96]; n = 887 women), but the certainty of evidence is low to very low. With low-dose myo-inositol however, evidence is uncertain about its benefit on the incidence of gestational diabetes mellitus in overweight and obese women with RR 0.71; CI [0.14, 3.50]. No adverse effects were noted. For the secondary outcomes, standard dose myo-inositol appears to reduce the incidence of pregnancy-induced hypertension and preterm delivery, but the certainty of evidence is low to very low. Conclusion Current evidence is uncertain on the potential benefit of myo-inositol supplementation in overweight and obese pregnant women. While studies show that 4 g myo-inositol per day may decrease the incidence of GDM, pregnancy-induced hypertension and pre-term birth with no associated risk of serious adverse events, the certainty of evidence is low to very low. Future high-quality trials may provide more compelling evidence to support practice recommendations.
Diabetes, Gestational ; Obesity ; Inositol Phosphates

Inositol 1,4,5-trisphosphate receptors (InsP3Rs) modulate Ca2+ release from intracellular Ca2+ store and are extensively expressed in the membrane of endoplasmic/sarcoplasmic reticulum and Golgi. Although caffeine and 2-aminoethoxydiphenyl borate (2-APB) have been widely used to block InsP3Rs, the use of these is limited due to their multiple actions. In the present study, we examined and compared the ability of caffeine and 2-APB as a blocker of Ca2+ release from intracellular Ca2+ stores and Ca2+ entry through store-operated Ca2+ (SOC) channel in the mouse pancreatic acinar cell. Caffeine did not block the Ca2+ entry, but significantly inhibited carbamylcholine (CCh)-induced Ca2+ release. In contrast, 2-APB did not block CCh-induced Ca2+ release, but remarkably blocked SOC-mediated Ca2+ entry at lower concentrations. In permeabilized acinar cell, caffeine had an inhibitory effect on InsP3-induced Ca2+ release, but 2-APB at lower concentration, which effectively blocked Ca2+ entry, had no inhibitory action. At higher concentrations, 2-APB has multiple paradoxical effects including inhibition of InsP3-induced Ca2+ release and direct stimulation of Ca2+ release. Based on the results, we concluded that caffeine is useful as an inhibitor of InsP3R, and 2-APB at lower concentration is considered a blocker of Ca2+ entry through SOC channels in the pancreatic acinar cell.
Acinar Cells ; Animals ; Boron Compounds ; Caffeine ; Calcium ; Carbachol ; Inositol 1,4,5-Trisphosphate Receptors ; Membranes ; Mice ; Reticulum

In the present study, it was aimed to further identify the intracellular action mechanism of cromakalim and levcromakaliin in the porcine coronary artery. In intact porcine coronary arterial strips loaded with fura-2/AM, acetylcholine caused an increase in intracellular free Ca2+ ((Ca2+)-i) in association with a contraction in a concentration-dependent manner. Cromakalim (1 micrometer) caused a reduction in acetylcholine-induced increased (Ca2+)-i not only in the normal physiological salt solution (PSS) but also in Ca2+ -free PSS (containing 1mM EGTA). In the skinned strips prepared by exposure of tissue to 20 micrometer beta-escin, inositol 1,4,5-trisphosphate (IP-3) evoked an increase in (Ca2+)-i but it was without effect on the intact strips. The IP-3-induced increase in (Ca2+)-i was inhibited by cromakalim by 78% and levcromakalim by 59% (1 micrometer, each). Pretreatment with glibenclamide (a blocker of ATP-sensitive K+ channels, 10 micrometer and apamin (a blocker of small conductance Ca2+/-activated K+ channels, 1 micrometer strongly blocked the effect of cromakalim and levcromakalim. However, charybdotoxin (a blocker of large conductance Ca2+ -activated K+ channels, 1-micrometer) was without effect. In addition, cromakalim inhibited the GTP-gamma-S (100 micrometer, nonhydrolysable analogue of GTP)-induced increase in (Ca2+)-i. Based on these results, it is suggested that cromakalim and levcromakalim exert a potent vasorelaxation, in part, by acting on the K+ channels of the intracellular sites (e.g., sarcoplasmic reticulum membrane), thereby, resulting in decrease in release of Ca2+ from the intracellular storage site.
Acetylcholine ; Apamin ; Charybdotoxin ; Coronary Vessels* ; Cromakalim* ; Escin ; Glyburide ; Inositol 1,4,5-Trisphosphate ; Sarcoplasmic Reticulum ; Skin ; Vasodilation

OBJECTIVE: To explore the clinical and genetic characteristics of a child with spinocerebellar ataxia type 29 (SCA29) due to novel variant of the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) gene. METHODS: The child was subjected high-throughput sequencing, and candidate variant was verified by Sanger sequencing of his family members. RESULTS: The child was found to harbor a c.800C>T (p.T267M) variant of the ITPR1 gene, which was not found in his parents and their fetus. The variant has occurred in a hotspot of the ITPR1 gene variants and was unreported before in China. Based on his clinical and genetic characteristics, the child was diagnosed with SCA29. CONCLUSION The novel heterozygous c.800C>T (p.T267M) of the ITPR1 gene probably underlay the SCA29 in this child.
Child ; Humans ; Family ; Inositol 1,4,5-Trisphosphate Receptors/genetics* ; Mutation ; Spinocerebellar Ataxias/genetics* ; Spinocerebellar Degenerations

In this study, the effect of systemic administration of kainic acid (KA) on the expression of inositol 1,4,5-trisphosphate receptor mRNA in the rat brain was investigated with in situ hybridization histochemistry. After the injection of KA in a convulsive dose (10 mg/kg i.p.), inositol 1,4,5-trisphosphate receptor mRNA was reduced significantly in dentate gyrus, cerebral cortex, and caudate-putamen and moderately in CA1-CA3 areas of hippocampus and cerebellum. In dentate gyrus, the expression of inositol 1,4,5-trisphosphate receptor mRNA was significantly decreased at 6 h, lowest level at 9 h, after that the expression was gradually recovered and returned to basal level at 72 h after KA injection. However, in the CA1-CA3 areas of the hippocampus, cerebral cortex, and caudate-putamen, the expression of inositol 1,4,5-trisphosphate receptor mRNA was abruptly decreased at 9 h and almost return to basal level at 24 h after KA injection. The significant repression of inositol 1,4,5-trisphosphate receptor mRNA in cerebellum was only found at 9 h after KA injection. But significant change of inositol 1,4,5-trisphosphate receptor mRNA was not found in the brains of rats treated with NMDA receptor blocker, MK-801, followed by KA injection. These observations suggest that the inositol 1,4,5-trisphosphate receptor is one of the genes whose expression can be altered by KA treatment and the NMDA receptor is related with this alternation.
Animals ; Brain* ; Cerebellum ; Cerebral Cortex ; Dentate Gyrus ; Dizocilpine Maleate ; Hippocampus ; In Situ Hybridization ; Inositol 1,4,5-Trisphosphate* ; Inositol* ; Kainic Acid* ; N-Methylaspartate ; Rats* ; Repression, Psychology ; RNA, Messenger* ; Seizures*