Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels

2006 ◽  
Vol 291 (4) ◽  
pp. C726-C739 ◽  
Author(s):  
Monica C. Chen ◽  
S. Vincent Wu ◽  
Joseph R. Reeve ◽  
Enrique Rozengurt
Keyword(s):  
Endocrine Cells ◽  
Bitter Taste ◽  
Dependent Manner ◽  
Gi Tract ◽  
Intracellular Ca ◽  
Α Subunits ◽  
Ca2 Channels ◽  
Cck Release

We previously demonstrated the expression of bitter taste receptors of the type 2 family (T2R) and the α-subunits of the G protein gustducin (Gαgust) in the rodent gastrointestinal (GI) tract and in GI endocrine cells. In this study, we characterized mechanisms of Ca2+ fluxes induced by two distinct T2R ligands: denatonium benzoate (DB) and phenylthiocarbamide (PTC), in mouse enteroendocrine cell line STC-1. Both DB and PTC induced a marked increase in intracellular [Ca2+] ([Ca2+]i) in a dose- and time-dependent manner. Chelating extracellular Ca2+ with EGTA blocked the increase in [Ca2+]i induced by either DB or PTC but, in contrast, did not prevent the effect induced by bombesin. Thapsigargin blocked the transient increase in [Ca2+]i induced by bombesin, but did not attenuate the [Ca2+]i increase elicited by DB or PTC. These results indicate that Ca2+ influx mediates the increase in [Ca2+]i induced by DB and PTC in STC-1 cells. Preincubation with the L-type voltage-sensitive Ca2+ channel (L-type VSCC) blockers nitrendipine or diltiazem for 30 min inhibited the increase in [Ca2+]i elicited by DB or PTC. Furthermore, exposure to the L-type VSCCs opener BAY K 8644 potentiated the increase in [Ca2+]i induced by DB and PTC. Stimulation with DB also induced a marked increase in the release of cholecystokinin from STC-1 cells, an effect also abrogated by prior exposure to EGTA or L-type VSCC blockers. Collectively, our results demonstrate that bitter tastants increase [Ca2+]i and cholecystokinin release through Ca2+ influx mediated by the opening of L-type VSCCs in enteroendocrine STC-1 cells.

scholarly journals The Emerging Role of Polyphenols in the Management of Type 2 Diabetes

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 703
Author(s):  
Yao Wang ◽  
Hana Alkhalidy ◽  
Dongmin Liu
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Homeostasis ◽  
Gut Hormones ◽  
Nutritional Regulation ◽  
Gi Tract ◽  
Cell Dysfunction ◽  
Glucagon Like Peptide 1 ◽  
Metabolic Action

Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic β-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells plays a pivotal role in maintaining glucose homeostasis via eliciting pleiotropic effects, which are largely mediated via its receptor. Thus, targeting the GLP-1 signaling system is a highly attractive therapeutic strategy to treatment T2D. Polyphenols, the secondary metabolites from plants, have drawn considerable attention because of their numerous health benefits, including potential anti-diabetic effects. Although the major targets and locations for the polyphenolic compounds to exert the anti-diabetic action are still unclear, the first organ that is exposed to these compounds is the GI tract in which polyphenols could modulate enzymes and hormones. Indeed, emerging evidence has shown that polyphenols can stimulate GLP-1 secretion, indicating that these natural compounds might exert metabolic action at least partially mediated by GLP-1. This review provides an overview of nutritional regulation of GLP-1 secretion and summarizes recent studies on the roles of polyphenols in GLP-1 secretion and degradation as it relates to metabolic homeostasis. In addition, the effects of polyphenols on microbiota and microbial metabolites that could indirectly modulate GLP-1 secretion are also discussed.

L-type Ca2+ channels in fetal and adult ovine cerebral arteries

2002 ◽  
Vol 282 (1) ◽  
pp. R131-R138 ◽  
Author(s):  
Arlin B. Blood ◽  
Yu Zhao ◽  
Wen Long ◽  
Lubo Zhang ◽  
Lawrence D. Longo
Keyword(s):  
Carotid Arteries ◽  
Cerebral Arteries ◽  
Bay K 8644 ◽  
Channel Density ◽  
Immunoblotting Assay ◽  
Intracellular Ca ◽  
Common Carotid Arteries ◽  
Fetal Vessels ◽  
Ca2 Channels

Recently, we reported that, whereas in cerebral arteries of the adult a majority of norepinephrine (NE)-induced increase in intracellular Ca2+ concentration ([Ca2+]i) comes from release of the sarcoplasmic reticulum (SR) Ca2+ stores, in the fetus the SR Ca2+ stores are relatively small, and NE-induced increase in [Ca2+]i results mainly from activation of plasma membrane L-type Ca2+ channels (20). In an effort to establish further the role of L-type Ca2+ channels in the developing cerebral arteries, we tested the hypothesis that, in the fetus, increased reliance on plasmalemmal L-type Ca2+ channels is mediated, in part, by increased L-type Ca2+ channel density. We used3H-labeled (+)isopropyl-4-(2,1,3-benzoxadiazol-4-y1)-1,4-dihydro-(2,6-dimethyl-5-methoxycarbonyl)pyridine-3-carboxylate (PN200–110, isradipine) to measure L-type Ca2+ channel density (Bmax) in the cerebral arteries, common carotid artery (CCA), and descending aortae of fetal (∼140 gestation days), newborn (7–10 days), and adult sheep. In the cerebral and common carotid arteries, Bmax values (fmol/mg protein) of fetuses and newborns were significantly greater than those of adults. Western immunoblotting assay also revealed that the density of L-type Ca2+ channel protein in the cerebral arteries and CCA was about twofold greater in the fetus than the adult. Finally, compared with the adult, fetal cerebral arteries demonstrated a significantly greater maximum tension and [Ca2+]i in response to stimulation with the L-type Ca2+ channel agonist Bay K 8644. In addition, Bay K 8644-stimulated fetal vessels demonstrated a maximal tension and [Ca2+]isimilar to that observed in response to stimulation with 10−4 NE. These results support the idea that fetal cerebrovascular smooth muscle relies more on extracellular Ca2+ and L-type Ca2+ channels for contraction than does the adult and that this increased reliance is mediated, in part, by greater L-type Ca2+ channel density. This may have important implications in the regulation of cerebral blood flow in the developing organism.

TRPC4 forms store-operated Ca2+ channels in mouse mesangial cells

2004 ◽  
Vol 287 (2) ◽  
pp. C357-C364 ◽  
Author(s):  
Xiaoxia Wang ◽  
Jennifer L. Pluznick ◽  
Peilin Wei ◽  
Babu J. Padanilam ◽  
Steven C. Sansom
Keyword(s):  
Transient Receptor Potential ◽  
Mesangial Cells ◽  
Receptor Potential ◽  
Immunocytochemical Staining ◽  
Rt Pcr ◽  
Fura 2 ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Ca2 Channels

Studies were performed to identify the molecular component responsible for store-operated Ca2+ entry in murine mesangial cells (MMC). Because the canonical transient receptor potential (TRPC) family of proteins was previously shown to comprise Ca2+-selective and -nonselective cation channels in a variety of cells, we screened TRPC1–TRPC7 with the use of molecular methods and the fura 2 method to determine their participation as components of the mesangial store-operated Ca2+ (SOC) channel. Using TRPC-specific primers and RT-PCR, we found that cultured MMC contained mRNA for TRPC1 and TRPC4 but not for TRPC2, TRPC3, TRPC5, TRPC6, and TRPC7. Immunocytochemical staining of MMC revealed predominantly cytoplasmic expression of TRPC1 and plasmalemmal expression of TRPC4. The role of TRPC4 in SOC was determined with TRPC4 antisense and fura 2 ratiometric measurements of intracellular Ca2+ concentration ([Ca2+]i). SOC was measured as the increase in [Ca2+]i after extracellular Ca2+ was increased from <10 nM to 1 mM in the continued presence of thapsigargin. We found that TRPC4 antisense, which reduced plasmalemmal expression of TRPC4, inhibited SOC by 83%. Incubation with scrambled TRPC4 oligonucleotides did not affect SOC. Immunohistochemical staining identified expressed TRPC4 in the glomeruli of mouse renal sections. The results of RT-PCR performed to distinguish between TRPC4-α and TRPC4-β were consistent with expression of both isoforms in brain but with only TRPC4-α expression in MMC. These studies show that TRPC4-α may form the homotetrameric SOC in mouse mesangial cells.

Activation of Phosphatidylinositol-Linked Novel D1 Dopamine Receptors Inhibits High-Voltage-Activated Ca2+ Currents in Primary Cultured Striatal Neurons

2009 ◽  
Vol 101 (5) ◽  
pp. 2230-2238 ◽  
Author(s):  
Li-Qun Ma ◽  
Chao Liu ◽  
Fang Wang ◽  
Na Xie ◽  
Jun Gu ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
High Voltage ◽  
Dependent Manner ◽  
Striatal Neurons ◽  
Inhibitory Effects ◽  
Patch Clamp Technique ◽  
Whole Cell Patch Clamp ◽  
Intracellular Ca ◽  
Dose Dependent

Recent evidences indicate the existence of a putative novel phosphatidylinositol (PI)-linked D1 dopamine receptor that mediates excellent anti-Parkinsonian but less severe dyskinesia action. To further understand the basic physiological function of this receptor in brain, the effects of a PI-linked D1 dopamine receptor-selective agonist 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) on high-voltage activated (HVA) Ca2+ currents in primary cultured striatal neurons were investigated by whole cell patch-clamp technique. The results indicated that stimulation by SKF83959 induced an inhibition of HVA Ca2+ currents in a dose-dependent manner in substance-P (SP)-immunoreactive striatal neurons. Application of D1 receptor, but not D2, α1 adrenergic, 5-HT receptor, or cholinoceptor antagonist prevented SKF83959-induced reduction, indicating that a D1 receptor-mediated event assumed via PI-linked D1 receptor. SKF83959-induced inhibitory modulation was mediated by activation of phospholipase C (PLC), mobilization of intracellular Ca2+ stores and activation of calcineurin. Furthermore, the inhibitory effects were attenuated significantly by the L-type calcium channel antagonist nifedipine, suggesting that L-type calcium channels involved in the regulation induced by SKF83959. These findings may help to further understand the functional role of the PI-linked dopamine receptor in brain.

scholarly journals Platelets, Not an Insignificant Player in Development of Allergic Asthma

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2038
Author(s):  
Liping Luo ◽  
Junyan Zhang ◽  
Jongdae Lee ◽  
Ailin Tao
Keyword(s):  
Allergic Asthma ◽  
Dependent Manner ◽  
Chronic Inflammatory Response ◽  
Gm Csf ◽  
Type 2 Immune Response ◽  
Asthma Patients ◽  
Ige Mediated ◽  
Dependent Mechanism

Allergic asthma is a chronic and heterogeneous pulmonary disease in which platelets can be activated in an IgE-mediated pathway and migrate to the airways via CCR3-dependent mechanism. Activated platelets secrete IL-33, Dkk-1, and 5-HT or overexpress CD40L on the cell surfaces to induce Type 2 immune response or interact with TSLP-stimulated myeloid DCs through the RANK-RANKL-dependent manner to tune the sensitization stage of allergic asthma. Additionally, platelets can mediate leukocyte infiltration into the lungs through P-selectin-mediated interaction with PSGL-1 and upregulate integrin expression in activated leukocytes. Platelets release myl9/12 protein to recruit CD4+CD69+ T cells to the inflammatory sites. Bronchoactive mediators, enzymes, and ROS released by platelets also contribute to the pathogenesis of allergic asthma. GM-CSF from platelets inhibits the eosinophil apoptosis, thus enhancing the chronic inflammatory response and tissue damage. Functional alterations in the mitochondria of platelets in allergic asthmatic lungs further confirm the role of platelets in the inflammation response. Given the extensive roles of platelets in allergic asthma, antiplatelet drugs have been tested in some allergic asthma patients. Therefore, elucidating the role of platelets in the pathogenesis of allergic asthma will provide us with new insights and lead to novel approaches in the treatment of this disease.

Characterizing voltage-dependent Ca2+ channels coupled to VIP release and NO synthesis in enteric synaptosomes

2002 ◽  
Vol 283 (5) ◽  
pp. G1027-G1034 ◽  
Author(s):  
M. Kurjak ◽  
A. Sennefelder ◽  
M. Aigner ◽  
V. Schusdziarra ◽  
H. D. Allescher
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Channel Blockers ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
P Type ◽  
Ca2 Channels

In enteric synaptosomes of the rat, the role of voltage-dependent Ca2+channels in K+-induced VIP release and nitric oxide (NO) synthesis was investigated. Basal VIP release was 39 ± 4 pg/mg, and cofactor-substituted NO synthase activity was 7.0 ± 0.8 fmol · mg−1 · min−1. K+ depolarization (65 mM) stimulated VIP release Ca2+ dependently (basal, 100%; K+, 172.2 ± 16.2%; P < 0.05, n = 5). K+-stimulated VIP release was reduced by blockers of the P-type (ω-agatoxin-IVA, 3 × 10−8 M) and N-type (ω-conotoxin-GVIA, 10−6 M) Ca2+ channels by ∼50 and 25%, respectively, but not by blockers of the L-type (isradipine, 10−8 M), Q-type (ω-conotoxin-MVIIC, 10−6 M), or T-type (Ni2+, 10−6 M) Ca2+ channels. In contrast, NO synthesis was suppressed by ω-agatoxin-IVA, ω-conotoxin-GVIA, and isradipine by ∼79, 70, and 70%, respectively, whereas Ni2+ and ω-conotoxin-MVIIC had no effect. These findings are suggestive of a coupling of depolarization-induced VIP release primarily to the P- and N-type Ca2+ channels, whereas NO synthesis is presumably dependent on Ca2+ influx not only via the P- and N- but also via the L-type Ca2+ channel. In contrast, none of the Ca2+ channel blockers affected VIP release evoked by exogenous NO, suggesting that NO induces VIP secretion by a different mechanism, presumably involving intracellular Ca2+ stores.

Endogenous cholecystokinin drives gallbladder emptying in dogs

1986 ◽  
Vol 251 (4) ◽  
pp. G553-G558
Author(s):  
K. Shiratori ◽  
S. Watanabe ◽  
W. Y. Chey ◽  
K. Y. Lee ◽  
T. M. Chang
Keyword(s):  
Corn Oil ◽  
Venous Blood ◽  
Gallbladder Emptying ◽  
Dependent Manner ◽  
Gallbladder Volume ◽  
Dose Dependent ◽  
Intraduodenal Administration ◽  
Different Doses ◽  
Cck Release

We investigated the effect of fat in the duodenum on the gallbladder emptying in seven dogs prepared with gastric, duodenal, and gallbladder cannulas. Gallbladder volume was measured at 15-min intervals, and venous blood samples were obtained at regular intervals for 2.5 h. Intraduodenal administration of Lipomul (pH 5.0, corn oil) in three different doses (1.1, 2.2, and 4.4 mmol/10 min) resulted in significant increases in gallbladder emptying in a dose-dependent manner (r = 0.8668, P less than 0.001). Likewise, the increase in integrated cholecystokinin (CCK) release in response to Lipomul was also dose dependent (r = 0.7334, P less than 0.001). A statistically significant correlation was found between integrated CCK release and gallbladder emptying in response to Lipomul (P less than 0.001). To determine the role of circulating endogenous CCK on gallbladder emptying effects of intravenous administration of proglumide and a rabbit anti-CCK serum on gallbladder emptying were studied. Gallbladder emptying was virtually abolished by the antiserum. Proglumide not only abolished the emptying but also increased gallbladder volume. Thus we conclude that in dogs the gallbladder emptying in response to fat in the upper small intestine depends on increased circulating endogenous CCK.

Deltamethrin-Induced Immunotoxicity and its Protection by Quercetin: An Experimental Study

2020 ◽  
Vol 20 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Anoop Kumar ◽  
Meenakshi Gupta ◽  
Ruchika Sharma ◽  
Neelima Sharma
Keyword(s):  
In Silico ◽  
Immune Cell ◽  
Protective Role ◽  
B Cell Receptors ◽  
Dependent Manner ◽  
Cell Receptors ◽  
In Vitro Techniques

Background: Deltamethrin (DLM) is a type 2 pyrethroid insecticide used in agriculture and home to control pests. However, emerging reports have indicated the immunotoxicity of DLM. Objective: Thus, in the current investigation, we have checked the immune-protective role of quercetin in DLM-induced immunotoxicity by using in silico and in vitro techniques. Results: In silico results have shown good interaction of quercetin towards immune cell receptors (T & B cell receptors). The findings of in vitro studies indicated the decrease in oxidative stress which is elevated by DLM in concentration & time-dependent manner. The increased caspases-3 activity was decreased by treatment of quercetin. The apoptosis induced by DLM in thymus and spleen was suppressed only at higher concentration (50μg/ml) of quercetin. Finally, the phenotypic changes due to DLM were restored by quercetin. Conclusion: Quercetin has strong binding affinity towards CD4, CD8 and CD28, CD45 receptors and protects the thymocytes and splenocytes against DLM-induced apoptotic signaling pathways.

Regulation of mouse egg activation: presence of ryanodine receptors and effects of microinjected ryanodine and cyclic ADP ribose on uninseminated and inseminated eggs

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2233-2244 ◽  
Author(s):  
T. Ayabe ◽  
G.S. Kopf ◽  
R.M. Schultz
Keyword(s):  
Ryanodine Receptor ◽  
Ryanodine Receptors ◽  
Meiotic Spindle ◽  
Egg Activation ◽  
Dependent Manner ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate ◽  
Mouse Egg

Sperm-induced activation of mammalian eggs is associated with a transient increase in Ca2+ concentrations thought to be derived from inositol 1,4,5-trisphosphate-sensitive and -insensitive intracellular stores. Whereas the importance of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores has been evaluated, the identity and role of inositol 1,4,5-trisphosphate-insensitive stores are poorly understood. To explore the role of the ryanodine-sensitive Ca2+ store, we first used reverse transcription-polymerase chain reaction to identify transcripts of the ryanodine receptor in eggs and determined that transcripts for the type 2 and 3 receptor were present. Immunoprecipitation of radioiodinated egg extracts with an antibody that recognizes both type 2 and 3 receptors detected specifically a band of Mr = 520,000. Immunolocalization of the receptor(s) using laser-scanning confocal microscopy revealed that the receptor(s) was uniformly distributed in the cortex of the germinal vesicle-intact oocyte, but became asymmetrically localized to the cortex in a region apposed to the meiotic spindle in the metaphase II-arrested egg; this asymmetrical localization developed by metaphase I. The role of the ryanodine receptor in mouse egg activation was examined by determining the effects of microinjected ryanodine or cyclic ADP ribose on endpoints of egg activation in either uninseminated or inseminated eggs. Ryanodine induced the conversion of the zona pellucida glycoprotein ZP2 to its postfertilization form ZP2f in a biphasic concentration-dependent manner; nanomolar concentrations stimulated this conversion, whereas micromolar concentrations had no stimulatory effect. Cyclic ADP ribose also promoted the ZP2 conversion, but with a hyperbolic concentration dependence. Neither of these compounds induced cell cycle resumption. Inhibiting the inositol 1,4,5-trisphosphate-sensitive Ca2+ store did not inhibit the ryanodine-induced ZP2 conversion and, reciprocally, inhibiting the ryanodine-sensitive Ca2+ store did not inhibit the inositol 1,4,5-trisphosphate-induced ZP2 conversion. Last, treatment of eggs under conditions that would block the release of Ca2+ from the ryanodine-sensitive store had no effect on any event of egg activation following fertilization. Results of these experiments suggest that although ryanodine receptors are present and functional, release of Ca2+ from this store is not essential for sperm-induced egg activation.

Role of AT2 receptor in the brain in regulation of blood pressure and water intake

2003 ◽  
Vol 284 (1) ◽  
pp. H116-H121 ◽  
Author(s):  
Zhen Li ◽  
Masaru Iwai ◽  
Lan Wu ◽  
Tetsuya Shiuchi ◽  
Toyohisa Jinno ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Water Intake ◽  
Pressor Response ◽  
Receptor Blocker ◽  
Dependent Manner ◽  
Ang Ii ◽  
Dose Dependent ◽  
Regulation Of Blood Pressure

The effects of intracerebroventricular (ICV) injection of angiotensin II (ANG II) on blood pressure and water intake were examined with the use of ANG II receptor-deficient mice. ICV injection of ANG II increased systolic blood pressure in a dose-dependent manner in wild-type (WT) mice and ANG type 2 AT2 receptor null (knockout) (AT2KO) mice; however, this increase was significantly greater in AT2KO mice than in WT mice. The pressor response to a central injection of ANG II in WT mice was inhibited by ICV preinjection of the selective AT1 receptor blocker valsartan but exaggerated by the AT2 receptor blocker PD-123319. ICV injection of ANG II also increased water intake. It was partly but significantly suppressed both in AT2KO and AT1aKO mice. Water intake in AT2/AT1aKO mice did not respond to ICV injection of ANG II. Both valsartan and PD-123319 partly inhibited water intake in WT mice. These results indicate an antagonistic action between central AT1a and AT2 receptors in the regulation of blood pressure, but they act synergistically in the regulation of water intake induced by ANG II.

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