scholarly journals Tocopherol esters inhibit human glutathione S-transferase omega.

2006 ◽  
Vol 53 (3) ◽  
pp. 547-552 ◽  
Author(s):  
Adriana Sampayo-Reyes ◽  
Robert A Zakharyan
Keyword(s):  
Vitamin E ◽  
Neurodegenerative Diseases ◽  
Alpha Tocopherol ◽  
Dependent Manner ◽  
Cytokine Release ◽  
Glutathione S Transferase ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Gst Family ◽  
Burk Plot

Human glutathione S-transferase omega 1-1 (hGSTO1-1) is a newly identified member of the glutathione S-transferase (GST) family of genes, which also contains alpha, mu, pi, sigma, theta, and zeta members. hGSTO1-1 catalyzes the reduction of arsenate, monomethylarsenate (MMA(V)), and dimethylarsenate (DMA(V)) and exhibits thioltransferase and dehydroascorbate reductase activities. Recent evidence has show that cytokine release inhibitory drugs, which specifically inhibit interleukin-1b (IL-1b), directly target hGSTO1-1. We found that (+)-alpha-tocopherol phosphate and (+)-alpha-tocopherol succinate inhibit hGSTO1-1 in a concentration-dependent manner with IC50 values of 2 microM and 4 microM, respectively. A Lineweaver-Burk plot demonstrated the uncompetitive nature of this inhibition. The molecular mechanism behind the inhibition of hGSTO1-1 by alpha-tocopherol esters (vitamin E) is important for understanding neurodegenerative diseases, which are also influenced by vitamin E.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

Cytotoxic Effects of Ferula Latisecta on Human Glioma U87 Cells

Drug Research ◽  
2019 ◽  
Vol 69 (12) ◽  
pp. 665-670 ◽  
Author(s):  
Mohammad Jalili-Nik ◽  
Hamed Sabri ◽  
Ehsan Zamiri ◽  
Mohammad Soukhtanloo ◽  
Mostafa Karimi Roshan ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Gelatin Zymography ◽  
Annexin V ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
Natural Herb ◽  
First Time ◽  
U87 Cells

AbstractGlioblastoma multiforme (GBM) is the fatal type of astrocytic tumors with a survival rate of 12 months. The present study, for the first time, evaluated the cytotoxic impacts of Ferula latisecta (F. latisecta) hydroalcoholic extract on U87 GBM cell line. The MTT assay measured the cellular toxicity following 24- and 48 h treatment with various doses of F. latisecta (0–800 μg/mL). Apoptosis was evaluated by an Annexin V/propidium iodide (PI) staining 24 h after treatment by F. latisecta. Moreover, to determine the cellular metastasis of U87 cells, we used a gelatin zymography assay (matrix metalloproteinase [MMP]-2/-9 enzymatic activity). The outcomes showed that F. latisecta mitigated the viability of U87 cells in a concentration- and time-dependent manner with IC50 values of 145.3 and 192.3 μg/mL obtained for 24- and 48 h treatments, respectively. F. latisecta induced apoptosis in a concentration-dependent manner after 24 h. Also, MMP-9 activity was significantly decreased following 24 h after treatment concentration-dependently with no change in MMP-2 enzymatic activity. This study showed that F. latisecta induced cytotoxicity and apoptosis, and mitigated metastasis of U87 GBM cells. Hence, F. latisecta could be beneficial as a promising natural herb against GBM after further studies.

scholarly journals COMT Effects on Vitamin E and Colorectal Cancer, in-vitro and in Two Randomized Trials (P15-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kathryn Hall ◽  
Stephanie Weinstein ◽  
Julie Buring ◽  
Kenneth Mukamal ◽  
M Vinayaga Moorthy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin E ◽  
Protein Expression ◽  
Randomized Clinical Trials ◽  
Alpha Tocopherol ◽  
Health Study ◽  
Dependent Manner ◽  
Family Protein ◽  
Low Activity

Abstract Objectives Despite promising observational data and compelling mechanisms of action, vitamin E has failed to demonstrate evidence of benefit in randomized clinical trials (RCTs). In two large long-term placebo-controlled RCTs, we reported that vitamin E effects on total cancer were modified by genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Here we investigate COMT effects on colorectal cancer (CRC) in the two RCTs and a CRC cell line. Methods We analyzed COMT rs4680 association with rates of CRC in the Women's Health Study (WHS), N = 23,294 and a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC). Cell survival and apoptosis were examined in-vitro in HCT116 cells treated with increasing doses of vitamin E when COMT gene expression was inhibited by silencing RNA (siRNA). Results Rates of CRC were higher with randomized vitamin E compared to placebo among COMT high-activity val/val homozygotes in ATBC (HR, [CI] = 3.00, [1.48–6.09]), but not WHS (HR, [CI] = 0.99, [0.63–1.57]). Among low-activity met/met homozygotes randomized to vitamin E compared to placebo, rates of CRC were borderline lower in WHS (HR, [CI] = 0.66, [0.44–1.01]), but not in ATBC (HR, [CI] = 0.93, [0.63–1.62]). In cell culture, vitamin E at 3 µg/ml and 10 µg/mL had no effect on cell viability or apoptosis. However, silencing COMT resulted in a modest apoptotic effect that vitamin E enhanced in a dose-dependent manner. Human apoptosis arrays indicated that in the absence of COMT expression, vitamin E induced protein expression related to the intrinsic apoptotic pathway through p53 activation, dysregulation of Bcl-2 family protein expression and down-regulation of IAP family protein expression. Conclusions Differential COMT effects on vitamin E and CRC were similar to those previously reported for all invasive cancers, but were only significant for val/val homozygotes. Further, inhibiting COMT in the presence of vitamin E in a CRC in-vitro model, recapitulated the RCT observation that among individuals homozygous for the low-activity allele (met/met) vitamin E tended to reduce invasive cancer and here CRC. Funding Sources National Institutes of Health: NCI and NHLBI.

scholarly journals Use of Parabens (Methyl and Butyl) during the Gestation Period: Mitochondrial Bioenergetics of the Testes and Antioxidant Capacity Alterations in Testes and Other Vital Organs of the F1 Generation

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1302
Author(s):  
Maria Manuel Oliveira ◽  
Fátima Martins ◽  
Mónica G. Silva ◽  
Elisete Correia ◽  
Romeu Videira ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Germ Cells ◽  
Citrate Synthase ◽  
Respiratory Control ◽  
Mitochondrial Bioenergetics ◽  
Dependent Manner ◽  
Glutathione S Transferase ◽  
Concentration Dependent Manner ◽  
Female Wistar Rats ◽  
F1 Generation

Since the mid-1920s, parabens have been widely used as antimicrobial preservatives in processed foods and beverages, pharmaceuticals, and cosmetic products. Paraben use continues to generate considerable controversy, both in the general population and in the scientific community itself. The primary purpose of our study was to determine whether parabens (methyl and butyl at concentrations of 100 and 200 mg/kg body weight by subcutaneous injection) during pregnancy of adult female Wistar rats can have an impact on the F1 generation. As far as we know, we are the first to demonstrate that using parabens during pregnancy has negative repercussions on the mitochondrial bioenergetics and antioxidant activity of testicular germ cells in the F1 generation. Our study showed that there was a 48.7 and 59.8% decrease in the respiratory control index with 100 and 200 mg/kg of butylparaben, respectively. Cytochrome c oxidase activity was significantly inhibited (45 and 51%) in both groups. In addition, 200 mg/kg butylparaben promoted a marked decrease in citrate synthase activity, indicating that mitochondrial content decreased in the germ cells, especially spermatocytes and spermatids. Mitochondrial ROS production increased in groups exposed to parabens in a concentration-dependent manner, especially the butyl one (102 and 130%). The groups exposed to butylparaben showed an increase in superoxide dismutase (SOD) and catalase (CAT) activities, while glutathione reductase (GR) and glutathione S-transferase (GST) decreased. With methylparaben, only differences in SOD and GR were observed; for the latter, this only occurred with the highest concentration. The glutathione (GSH)/glutathione disulfide (GSSG) ratio did not undergo any significant change. However, there was a considerable increase in hydroperoxide content in animals exposed to butylparaben, with 100 and 200 mg/kg resulting in 98.6 and 188% increase, respectively. Furthermore, several other organs also showed alterations in antioxidant capacity due to paraben use. In summary, our study demonstrates that paraben use during pregnancy will cause severe changes in the mitochondrial bioenergetics and antioxidant capacity of testicular germ cells and the antioxidant capacity of several other F1 generation organs.

scholarly journals Modulation of Calmodulin and Protein Kinase C Activities by Pencillium Mycotoxins

1999 ◽  
Vol 18 (2) ◽  
pp. 91-96 ◽  
Author(s):  
I. Pala ◽  
A. Srinivasan ◽  
P. J. S. Vig ◽  
D. Desaiah
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Complex Formation ◽  
Mammalian Brain ◽  
Dependent Manner ◽  
Active Conformation ◽  
Cellular Functions ◽  
Concentration Dependent Manner ◽  
Kinase C ◽  
Ic50 Values

Calmodulin (CaM), a calcium-binding protein, is found in high concentrations in mammalian brain where it plays a pivotal role in a large number of cellular functions. Protein kinase C (PKC), a multifunctional cytosolic enzyme, in the presence of both Ca2+ and phospholipids, transduce extracellular signals into intracellu-lar events. Both CaM and PKC are partially involved in maintaining Ca2+ homeostasis in the cell. Any fluctuations in the intracel-lular Ca2+ can modulate cellular functions and may contribute to neuronal dysfunction. Hence, the present investigation was initiated to study the effects of some selected penicillium (naturally occurring tremorgenic) mycotoxins like secalonic acid, citreoviridin, and verruculogen on CaM activity, active conformation of CaM and PKC activity. Stimulation of CaM-deflcient bovine brain 3′-5′ phosphodieste rase (PDE) indicated CaM activity. The modification of CaM active conformation was studied by the binding of fluorescent probe N-phenyl-1-napthylamine (NPN) to CaM. Alterations in the fluorescence of dansyl-CaM was used to study the effect of these compounds on complex formation between CaM and PDE. Rat brain cytosolic PKC was studied using 32P-ATP as a measure of altered protein phosphorylation. The concentrations of mycotoxins used were in the range of 10 to 50 μM. All three mycotoxins inhibited CaM-stimulated PDE activity in a concentration-dependent manner. Citreoviridin and secalonic acid inhibited NPN fluorescence and Ca2+-dependent complex formation of dansyl-CaM and PDE. The IC50 values for NPN fluorescence of citreoviridin and secalonic acid were 13 μM and 19 μM respectively. However, verruculogen showed little effect on NPN fluorescence and the Ca2+-dependent complex formation of dansyl-CaM and PDE. These mycotoxins also inhibited PKC activity in a concentration-dependent manner with IC50 values of 19.8, 25.7, and 38.4 μM for secalonic acid, citreoviridin, and verruculogen, respectively. The results of our study suggest that these mycotoxins at very low concentrations are interacting with CaM and PKC. Such an effect could lead to impairment of neurotransmission and result in neurotoxicity.

scholarly journals Constituents of Coreopsis lanceolata Flower and Their Dipeptidyl Peptidase IV Inhibitory Effects

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4370 ◽  
Author(s):  
Bo-Ram Kim ◽  
Sunil Paudel ◽  
Joo-Won Nam ◽  
Chang Jin ◽  
Ik-Soo Lee ◽  
...  
Keyword(s):  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Mass Spectrometry Data ◽  
Ionization Mass ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Dpp Iv ◽  
Ic50 Values ◽  
First Time

A new polyacetylene glycoside, (5R)-6E-tetradecene-8,10,12-triyne-1-ol-5-O-β-glucoside (1), was isolated from the flower of Coreopsis lanceolata (Compositae), together with two known compounds, bidenoside C (10) and (3S,4S)-5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-glucopyranoside (11), which were found in Coreopsis species for the first time. The other known compounds, lanceoletin (2), 3,2′-dihydroxy-4-3′-dimethoxychalcone-4′-glucoside (3), 4-methoxylanceoletin (4), lanceolin (5), leptosidin (6), (2R)-8-methoxybutin (7), luteolin (8) and quercetin (9), were isolated in this study and reported previously from this plant. The structure of 1 was elucidated by analyzing one-dimensional and two-dimensional nuclear magnetic resonance and high resolution-electrospray ionization-mass spectrometry data. All compounds were tested for their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and compounds 2–4, 6 and 7 inhibited DPP-IV activity in a concentration-dependent manner, with IC50 values from 9.6 to 64.9 μM. These results suggest that C. lanceolata flower and its active constituents show potential as therapeutic agents for diseases associated with type 2 diabetes mellitus.

scholarly journals Physicochemical, Structural, and Biological Properties of Polysaccharides from Dandelion

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1485 ◽  
Author(s):  
Huijing Guo ◽  
Weida Zhang ◽  
Ying Jiang ◽  
Hai Wang ◽  
Guogang Chen ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Biological Effects ◽  
Radical Scavenging ◽  
Water Soluble ◽  
Perennial Herb ◽  
Dependent Manner ◽  
Glycosidic Linkage ◽  
Food Ingredient ◽  
Concentration Dependent Manner ◽  
Ic50 Values

The edible and medicinal perennial herb dandelion is known to have antitumor, antioxidant, and anticomplement properties. However, the structural characterization and biological effects of its polysaccharides are not well understood. Here, we aimed to extract and investigate a novel polysaccharide from dandelion. A water-soluble polysaccharide, PD1-1, was successfully obtained from dandelion through ultrasonic-assisted extraction and purification using diethylaminoethyl (DEAE)–Sepharose fast flow and Sephadex G-75 columns. The results showed that PD1-1 is an inulin-type polysaccharide with a molecular weight of 2.6 kDa and is composed of glucose (52.39%), and mannose (45.41%). Glycosidic linkage analysis demonstrated that PD1-1 contains terminal α-d-Man/Glcp-(1→ and →1)-β-d-Man/Glcf-(2→ glycosidic linkage conformations. A physicochemical analysis indicated that PD1-1 has a triple helix structure and exhibits important properties, including good swelling, water-holding, and oil-holding capacities. Furthermore, PD1-1 showed good antioxidant activities in DPPH and hydroxyl free radical scavenging abilities, with IC50 values of 0.23 mg/mL and 0.25 mg/mL, respectively, and good hypoglycemic activities in α-amylase and α-glucosidase inhibition, with IC50 values of 0.53 mg/mL and 0.40 mg/mL, respectively, in a concentration-dependent manner. Results suggest that PD1-1 possesses efficacious antioxidant and hypoglycemic properties and has potential applications as a functional food ingredient.

scholarly journals EVALUATION OF IN VITRO CYTOTOXIC EFFECT OF VIOLACEIN PRODUCED BY NOVEL ISOLATE CHROMOBACTERIUM VACCINII CV5 AGAINST THE CERVICAL AND LUNG CANCER CELL

2017 ◽  
Vol 10 (10) ◽  
pp. 227 ◽  
Author(s):  
Vishnu T Santhosh ◽  
Palaniswamy Muthusamy
Keyword(s):  
Lung Cancer ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cytotoxicity Activity ◽  
Ic50 Values

  Objectives: This study investigates the in vitro anticancer activity of the violacein extracted from the Chromobacterium vaccinii CV5.Methods: Natural colorants or dyes derived from flora to fauna are believed to be safe because of nontoxic, noncarcinogenic, and biodegradable in nature. There are a number of natural pigments, but only a few are available in sufficient quantities for industrial production. The cytotoxicity activity of pigment was assessed against the cervical (HeLa) and lung cancer (A549) cell lines using the MTT assay and there by potential cytotoxic activity exhibited by the pigment was identified.Results: The result of the pigment shows potent anticancer activity on the two cancer cell lines tested in a concentration dependent manner. The potent anticancer activity was observed with the pigment with IC50 values of 26 μg/mL on HeLa and 31 μg/mL on A549 cells, respectively.Conclusion: The study is pioneering report for determining the better in vitro anticancer activity of violacein from the novel isolate C. vaccinii CV5.

Modulation of N-nitrosodiethylamine (NDEA) induced oxidative stress by vitamin E in rat erythrocytes

2005 ◽  
Vol 24 (6) ◽  
pp. 297-302 ◽  
Author(s):  
A K Bansal ◽  
M Bansal ◽  
G Soni ◽  
D Bhatnagar
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Enzyme Activities ◽  
Treated Group ◽  
Time Dependent ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Glutathione S Transferase ◽  
Rat Erythrocytes ◽  
Pre Treatment

Nitrosamines, such as N-nitrosodiethylamine (NDEA), induced oxidative stress due to the generation of reactive oxygen species, which are capable of initiating peroxidative damage to the cell. The present study was designed to establish whether pre-treatment with vitamin E (40 mg/kg body wt, intraperitoneally (ip), twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress caused by NDEA. A single necrogenic dose of NDEA (200 mg/kg body wt) was administered intraperitoneally (ip) to the rats with or without vitamin E pre-treatment and the animals were sacrificed on Day 7, 14 or 21 after NDEA administration. Lipid peroxidation (LPO) and the activities of antioxidant enzymes were determined in erythrocytes as indices of oxidative damage. The result showed elevated levels of LPO in erythrocytes with NDEA treatment, however, vitamin E pre-treated rats administered NDEA showed decreased LPO (Day 14 and 21). Superoxide dismutase (SOD) enzyme activity and the glutathione (GSH) content increased with NDEA treatment and remained high in vitamin E pre-treated group. Catalase (CAT), glutathione reductase (GSH-R) and glutathione-S-transferase (GST) enzyme activities declined with NDEA treatment; however, vitamin E pre-treated rats administered NDEA, showed elevation in the enzyme activities. Glutathione peroxidase (GSH-Px) activity increased in erythrocytes in vitamin E pre-treated rats administered NDEA, while SeGSH-Px activity was not affected significantly. This study demonstrates that the pre-treatment with vitamin E prior to the administration of NDEA was effective in counteracting and modulating oxidative stress in rat erythrocytes in a time-dependent manner.

scholarly journals Stereoselectivity of Ins(1,3,4,5)P4 recognition sites: implications for the mechanism of the Ins(1,3,4,5)P4-induced Ca2+ mobilization

1993 ◽  
Vol 294 (1) ◽  
pp. 191-194 ◽  
Author(s):  
R A Wilcox ◽  
R A Challiss ◽  
G Baudin ◽  
A Vasella ◽  
B V Potter ◽  
...  
Keyword(s):  
Binding Site ◽  
Specific Binding ◽  
Specific Interaction ◽  
Neuroblastoma Cells ◽  
Dependent Manner ◽  
Binding Studies ◽  
Concentration Dependent Manner ◽  
Human Neuroblastoma ◽  
Specific Binding Sites ◽  
Ic50 Values

Ins(1,3,4,5)P4 was able to mobilize the entire Ins(1,4,5)P3-sensitive intracellular Ca2+ store in saponin-permeabilized SH-SY5Y human neuroblastoma cells in a concentration-dependent manner, yielding an EC50 value of 2.05 +/- 0.45 microM, compared with 0.14 +/- 0.03 microM for Ins(1,4,5)P3. However, L-Ins(1,3,4,5)P4 [= D-Ins(1,3,5,6)P4] failed to cause mobilization of intracellular Ca2+ at concentrations up to 100 microM. Binding studies using pig cerebellar membranes as a source of both Ins(1,4,5)P3/Ins(1,3,4,5)P4-specific binding sites have revealed a marked contrast in their stereospecificity requirements. Ins(1,4,5)P3-receptors from pig cerebella exhibited stringent stereospecificity, L-Ins(1,4,5)P3 and L-Ins(1,3,4,5)P4 were > 1000-fold weaker, whereas Ins(1,3,4,5)P4 (IC50 762 +/- 15 nM) was only about 40-fold weaker than D-Ins(1,4,5)P3 (IC50 20.7 +/- 9.7 nM) at displacing specific [3H]Ins(1,4,5)P3 binding from an apparently homogeneous Ins(1,4,5)P3 receptor population. In contrast, the Ins(1,3,4,5)P4-binding site exhibited poor stereoselectivity. Ins(1,3,4,5)P4 produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding, with two-site analysis revealing KD values for high- and low-affinity sites of 2.1 +/- 0.5 nM and 918 +/- 161 nM respectively. L-Ins(1,3,4,5)P4 also produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding which was less than 10-fold weaker than with D-Ins(1,3,4,5)P4 (IC50 values for the high- and low-affinity sites of 17.2 +/- 3.7 nM and 3010 +/- 542 nM respectively). Therefore, although L-Ins(1,3,4,5)P4 appears to be a high-affinity Ins(1,3,4,5)P4-binding-site ligand in pig cerebellum, it is a very weak agonist at the Ca(2+)-mobilizing receptors of permeabilized SH-SY5Y cells. We suggest that the ability of D-Ins(1,3,4,5)P4 to access intracellular Ca2+ stores may derive from specific interaction with the Ins(1,4,5)P3- and not the Ins(1,3,4,5)P4-receptor population.

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