ATP stimulates Ca2+ mobilization by a nucleotide receptor in glomerular endothelial cells

1994 ◽  
Vol 266 (2) ◽  
pp. F210-F217 ◽  
Author(s):  
V. A. Briner ◽  
F. Kern
Keyword(s):  
Endothelial Cells ◽  
Receptor Agonist ◽  
Rank Order ◽  
P2y Receptors ◽  
Inhibitory Effect ◽  
P2x Receptor ◽  
Dependent Manner ◽  
Nucleotide Receptor ◽  
Pyrimidine Nucleotide ◽  
Glomerular Endothelial Cells

The present study investigates ATP effects on Ca2+ mobilization in bovine glomerular endothelial cells (GEC) and the receptors mediating ATP response. Extracellular ATP stimulated a rise in inositol 1,4,5-trisphosphate and cytosolic free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. Extracellular Ca2+ depletion did not prevent [Ca2+]i rise. ATP effects were not mediated by P1, P2x, and P2t purinoceptors, since the P1 receptor agonist adenosine and the P2x receptor agonist [alpha,beta-CH2]ATP had no effect on inositol 1-monophosphate (IP) formation and Ca2+ mobilization and ATP does not activate P2t receptors. The P2y receptor antagonist reactive blue (10(-3) M) had little inhibitory effect on ATP (10(-5) M)-stimulated IP formation (15.6 +/- 4.2%) and Ca2+ rise (7.0 +/- 3.0%). According to the classification of purinoceptors, ATP is less potent than 2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) in stimulating P2y receptors. In GEC, however, the rank order of potency in stimulating IP and [Ca2+]i rise was ATP > 2-MeS-ATP > ADP. The pyrimidine nucleotide UTP (10(-3) M) induced maximal IP formation (653 +/- 37%) and Ca2+ mobilization (591 +/- 22 nM) similar to ATP (IP 647 +/- 27%; [Ca2+]i 583 +/- 15 nM). At submaximal (10(-5) M) but not at maximal (10(-3) M) doses ATP and UTP effects were additive. ATP and UTP induced specific cross-desensitization. It is concluded that the purinergic nucleotide ATP and pyrimidine nucleotide UTP mediate their effects by a common nucleotide receptor. This receptor differs from P2z and P2y1 receptors, since by definition UTP does not activate these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine A1 receptor-mediated inhibition of vasopressin action in inner medullary collecting duct

1994 ◽  
Vol 266 (5) ◽  
pp. F791-F796 ◽  
Author(s):  
R. M. Edwards ◽  
W. S. Spielman
Keyword(s):  
Receptor Agonist ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Concentration Dependent Manner ◽  
Cgs 21680 ◽  
Camp Generation ◽  
A1 Receptor

We examined the effects of adenosine and adenosine analogues on arginine vasopressin (AVP)-induced increases in osmotic water permeability (Pf; micron/s) and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat inner medullary collecting ducts (IMCDs). When added to the bath, the A1 receptor agonist N6-cyclohexyladenosine (CHA) produced a rapid and reversible inhibition of AVP-stimulated (10 pM) Pf (1,781 +/- 195 to 314 +/- 85 microns/s at 0.3 microM CHA; n = 9). The inhibitory effect of CHA was concentration dependent, with a 50% inhibitory concentration of 10 nM. The effect of CHA was inhibited by prior exposure of IMCDs to the A1 receptor antagonist 1,3-dipropylxanthine-8-cyclopentylxanthine (DP-CPX; 1 microM) or by preincubation with pertussis toxin. CHA had no effect on cAMP-induced increases in Pf. In addition to CHA, adenosine and the nonselective agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) inhibited AVP-dependent Pf by > or = 70%, whereas the A2 receptor agonist CGS-21680 had no effect. Luminal adenosine (0.1 mM) had no effect on basal or AVP-stimulated Pf. CHA, NECA, and adenosine but not CGS-21680 inhibited AVP-stimulated cAMP accumulation in a concentration-dependent manner (50% inhibitory concentrations 0.1–300 nM). The inhibitory effect of CHA on AVP-stimulated cAMP accumulation was attenuated by DPCPX. We conclude that adenosine, acting at the basolateral membrane, inhibits AVP action in the IMCD via interaction with A1 receptors. The inhibition occurs proximal to cAMP generation and likely involves an inhibitory G protein.

scholarly journals Role of P2 receptors in vascular tone regulation

2016 ◽  
Vol 97 (3) ◽  
pp. 414-421
Author(s):  
B A Ziganshin ◽  
A A Spasov ◽  
A P Ziganshina ◽  
R K Dzhordzhikiya ◽  
A U Ziganshin
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Sympathetic Nerve ◽  
Vascular Tone ◽  
Muscle Cells ◽  
P2y Receptors ◽  
P2 Receptors ◽  
P2x Receptor ◽  
Nerve Terminals

P2 receptors, the main endogenous agonist of which is adenosine triphosphate (ATP), are widely distributed in mammalian tissues and organs, including the cardiovascular system. In human blood vessels, various types of the P2Y (metabotropic, G-protein coupled receptors) and P2X (ligand-gated ion channels) family of receptors are present. Several subtypes of P2X and P2Y receptors have been found on the surface of endothelial cells as well as smooth muscle cells of the vessels. Activation of various subtypes of P2 receptors located in different cells of the blood vessel can have multidirectional action on the tone of the vessel’s wall, thereby causing both vasoconstriction and vasodilatation. To date, two main physiologic mechanisms have been identified, via which Р2 receptors participate in controlling the vascular tone: (1) neuronal - ATP is released as a co-transmitter from perivascular sympathetic nerve terminals and activates P2 receptors located on vascular smooth muscle cells; (2) endothelial - ATP is released into the vessel’s lumen by endothelial cells and blood cells and activates P2 receptors located on the endothelial cells. In the first mechanism, simultaneous release of ATP and norepinephrine from sympathetic nerve terminals results in vasoconstriction caused by rapid depolarization, which is completely inhibited by P2X receptor antagonists, and slow depolarization, which is inhibited by alpha-adrenergic blockers. In the second mechanism, during shear stress and hypoxic conditions, ATP activates P2 receptors of endothelial cells causing vasodilatation. These differing effects, mediated via P2 receptors, make it very tempting to develop novel drugs that would regulate vascular tone via these receptors.

scholarly journals Pathological Hyperinsulinemia and Hyperglycemia in the Impaired Glucose Tolerance Stage Mediate Endothelial Dysfunction Through miR-21, PTEN/AKT/eNOS, and MARK/ET-1 Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Ran Liu ◽  
Shilin Guan ◽  
Zhongai Gao ◽  
Jingyu Wang ◽  
Jie Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Relative Concentration ◽  
Inhibitory Effect ◽  
Glomerular Endothelial Cells ◽  
High Insulin ◽  
The Individual

BackgroundImpaired glucose tolerance (IGT) is an important prediabetic stage characterized by elevated concentrations of glucose and insulin in the blood. The pathological hyperglycemia and hyperinsulinemia in IGT may regulate the expression of microRNA-21 (miR-21) and affect the downstream insulin signaling pathways, leading to endothelial cell dysfunction and early renal damage.MethodsThe individual and combined effects of insulin and glucose were investigated using human glomerular endothelial cells (HGECs). The expression levels of miR-21, and PTEN/AKT/eNOS and MAPK/ET-1 pathway proteins in the treated cells were measured. The levels of nitric oxide (NO) and endothelin-1 (ET-1) secreted by the cells were also measured. The role of miR-21 in mediating the regulatory effects of insulin and glucose was assessed by overexpression/inhibition of this miRNA using mimics/inhibitor.ResultsHigh (>16.7 mmol/L) concentration of glucose upregulated the expression of miR-21, leading to the activation and inhibition of the PTEN/AKT/eNOS and MAPK/ET-1 pathways, and upregulation of NO and downregulation of ET-1 secretion, respectively. High (>25 ng/mL) concentration of insulin downregulated the expression of miR-21, and lead to the activation of the MAPK/ET-1 and inhibition of the PTEN/AKT/eNOS pathway, thereby upregulating the expression of ET-1 and downregulating the secretion of NO. MiR-21 was observed to play a key role by directly controlling the activation of the insulin signaling pathways when the cells were cotreated with different concentrations of insulin and glucose. The expression of miR-21 was found to be dependent on the relative concentration of insulin and glucose. Under simulated conditions of the IGT stage (8.3 mmol/L glucose + 50 ng/mL insulin), the inhibitory effect of high insulin concentration on miR-21 expression in the cells attenuated the activation by high glucose concentration, resulting in the downregulation of miR-21, upregulation of ET-1 and downregulation of NO secretion.ConclusionTaken together, these results indicate that high insulin and glucose concentrations regulate the secretory function of glomerular endothelial cells in opposite ways by regulating the expression of miRNA-21. Pathological concentrations of insulin and glucose in the IGT stage may lead to a decrease in miR-21 expression, thereby disordering the secretion of vasoactive factors, resulting in renal tubule ischemia.

Permeability of endothelial monolayers to albumin is increased by bradykinin and inhibited by prostaglandins

2001 ◽  
Vol 280 (4) ◽  
pp. L732-L738 ◽  
Author(s):  
Pierre J. Farmer ◽  
Sylvie G. Bernier ◽  
Andrée Lepage ◽  
Gaétan Guillemette ◽  
Domenico Regoli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adenylate Cyclase ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Intracellular Level ◽  
Concentration Dependent Manner ◽  
Aortic Endothelial Cells ◽  
Endothelial Monolayers ◽  
Bovine Aortic Endothelial Cells

Using monolayers of bovine aortic endothelial cells (BAEC) in modified Boyden chambers, we examined the role of prostaglandins (PGs) in the bradykinin (BK)-induced increase of albumin permeability. BK induced a concentration-dependent increase of the permeability of BAEC, which reached 49.9 ± 1% at the concentration of 10−8 M. Two inhibitors of the prostaglandin G/H synthase, indomethacin (2.88 μM) and ibuprofen (10 μM), potentiated BK-induced permeability 1.8- and 3.9-fold, respectively. Exogenously administered PGE2and iloprost, a stable analog of prostacyclin, attenuated the effect of BK in a concentration-dependent manner. Butaprost equally reduced the effect of BK, suggesting the participation of the EP2receptor in this phenomenon. However, the EP4-selective antagonist AH-23848 did not significantly inhibit the protective effect of PGE2. The inhibitory effect of PGE2 was reversed by the adenylate cyclase inhibitor MDL-12330A (10 μM). These results suggest that BK-induced increase of permeability of BAEC monolayer to 125I-labeled albumin is negatively regulated by PGs. This postulated autocrine activity of PGs may involve an increase in the intracellular level of cAMP.

scholarly journals Inhibitory effect of serotonin derivatives on high glucose-induced adhesion and migration of monocytes on human aortic endothelial cells

2009 ◽  
Vol 102 (2) ◽  
pp. 264-272 ◽  
Author(s):  
Rosaria Piga ◽  
Yuji Naito ◽  
Satoshi Kokura ◽  
Osamu Handa ◽  
Toshikazu Yoshikawa
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Atherosclerotic Lesion ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Aortic Endothelial Cells ◽  
Serotonin Derivatives ◽  
And Migration ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

Previous reports have shown that safflower-seed extract and its major antioxidant constituents, serotonin hydroxycinnamic amides, attenuated atherosclerotic lesion formation in apoE-deficient mice, as well as inflammation and aortic stiffness in human subjects. In the present report, we examined a still unknown cell-based mechanism of serotonin derivatives against the development of atherosclerosis, focusing our attention on their action against the increase of adhesion molecules and the release of chemotactic factors on human aortic endothelial cells, phenomena that represent the key events in the early stages of atherosclerogenesis. Serotonin derivatives N-(p-coumaroyl)serotonin and N-feruloylserotonin exerted an inhibitory effect on short-term high glucose-induced up-regulation of mRNA and protein of adhesion and migration factors, and the consequent adhesion and migration of monocytes to endothelial cells; they inhibited the activation of transcription factors such as NF-κB, and the overproduction of the mitochondrial superoxide by acting as scavengers of the superoxide radical. In addition, serotonin derivative concentration inside the cells and inside the mitochondria was increased in a time-dependent manner. These results identify a mechanism of action of serotonin derivatives against endothelial damage at a cellular level, and underline their benefits against the disorders and complications related to reactive oxygen species.

scholarly journals Heterogeneity of pulmonary endothelial cyclic nucleotide response to Pseudomonas aeruginosa ExoY infection

2015 ◽  
Vol 309 (10) ◽  
pp. L1199-L1207 ◽  
Author(s):  
K. A. Morrow ◽  
R. Seifert ◽  
V. Kaever ◽  
A. L. Britain ◽  
S. L. Sayner ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Endothelial Cells ◽  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Rank Order ◽  
Dependent Manner ◽  
Gap Formation ◽  
Pulmonary Endothelium ◽  
Pulmonary Endothelial Cells ◽  
Intercellular Gaps

Here, we tested the hypothesis that a promiscuous bacterial cyclase synthesizes purine and pyrimidine cyclic nucleotides in the pulmonary endothelium. To test this hypothesis, pulmonary endothelial cells were infected with a strain of the Gram-negative bacterium Pseudomonas aeruginosa that introduces only exoenzyme Y (PA103 ΔexoUexoT::Tc pUCPexoY; ExoY+) via a type III secretion system. Purine and pyrimidine cyclic nucleotides were simultaneously detected using mass spectrometry. Pulmonary artery (PAECs) and pulmonary microvascular (PMVECs) endothelial cells both possess basal levels of four different cyclic nucleotides in the following rank order: cAMP > cUMP ≈ cGMP ≈ cCMP. Endothelial gap formation was induced in a time-dependent manner following ExoY+ intoxication. In PAECs, intercellular gaps formed within 2 h and progressively increased in size up to 6 h, when the experiment was terminated. cGMP concentrations increased within 1 h postinfection, whereas cAMP and cUMP concentrations increased within 3 h, and cCMP concentrations increased within 4 h postinfection. In PMVECs, intercellular gaps did not form until 4 h postinfection. Only cGMP and cUMP concentrations increased at 3 and 6 h postinfection, respectively. PAECs generated higher cyclic nucleotide levels than PMVECs, and the cyclic nucleotide levels increased earlier in response to ExoY+ intoxication. Heterogeneity of the cyclic nucleotide signature in response to P. aeruginosa infection exists between PAECs and PMVECs, suggesting the intracellular milieu in PAECs is more conducive to cNMP generation.

Glomerular endothelial cells respond to calcium-mobilizing agonists with release of EDRF

1990 ◽  
Vol 258 (5) ◽  
pp. F1295-F1303 ◽  
Author(s):  
P. A. Marsden ◽  
T. A. Brock ◽  
B. J. Ballermann
Keyword(s):  
Endothelial Cells ◽  
Calcium Concentration ◽  
Mesangial Cells ◽  
Platelet Activating Factor ◽  
Cytosolic Calcium ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Concentration Dependent Manner ◽  
Glomerular Function ◽  
Glomerular Endothelial Cells

To determine whether glomerular endothelial cells (GEN) may play a role in the local control of glomerular function by releasing endothelium-derived relaxing factor (EDRF), the effect of several agonists on GEN cytosolic calcium concentration ([Ca2+]i) and GEN EDRF release was determined. Bradykinin, ATP, thrombin, and platelet-activating factor (PAF) all increased [Ca2+]i in GEN in a concentration-dependent manner, whereas serotonin, acetylcholine, phenylephrine, and endothelin-1 were without effect. Coincubation of glomerular mesangial cells (GMC) with GEN augmented mesangial cell guanosine 3',5'-cyclic monophosphate (cGMP) content five- to sixfold, Bradykinin elicited a further concentration-dependent increase in GMC cGMP content in the presence but not absence of GEN. The GEN-dependent bradykinin-stimulated GMC cGMP accumulation was abolished by hemoglobin and methylene blue, blunted by gossypol, and augmented by superoxide dismutase. Other agonists capable of augmenting GEN [Ca2+]i also stimulated GMC cGMP accumulation in the presence but not in the absence of GEN. Thus cultured GEN release a factor that stimulates cGMP accumulation in adjacent mesangial cells which has the pharmacological characteristics of EDRF.

The Effect of Plant Polyphenol Genistein on Migration of Endothelial Cells Induced by Human Ovarian Carcinoma Cell Line SKOV3

2013 ◽  
Vol 781-784 ◽  
pp. 1156-1159
Author(s):  
Li Tang ◽  
Li Yu
Keyword(s):  
Endothelial Cells ◽  
Cell Line ◽  
Conditioned Medium ◽  
Inhibitory Effect ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Ovarian Carcinoma Cell Line ◽  
Skov3 Cells ◽  
Vessel Growth ◽  
And Migration

Angiogenesis is crucial for tumor progression and and migration of endothelial cells into tumor is important in the formation of new blood vessels in tumors. In this study we investigated the effect of Genistein on migration of human endothelial cells ECV-304 induced by human ovarian serous cystadenocarcinoma cell line SKOV3, and explored the mechanism of anti-angiogenesis of Genistein. Millicell chamber and coculture method were used to observe the influence on migration of ECV-304 induced by SKOV3 cells or its conditioned medium. The expression of angiogenesis associated protein VEGFbFGF and TGFβ-1 were determined using immunocytochemical assay. The results showed that either SKOV3 cells or its conditioned medium could induce the committed chemotactic migration of ECV-304. The chemotactic migrations of ECV-304 induced by SKOV3 or its conditioned medium were significantly inhibited by Genistein in a dose-dependent manner. 20μmol/L Genistein could down-regulate the expression of bFGF, and up-regulate the expression of TGFβ-1. Migrations of ECV-304 induced by SKOV3 or its conditioned medium are apparently inhibited by Genistein. It suggests that this inhibitory effect of Genistein is completed by down-regulating the expression of vessel growth-promoting factor bFGF, and up-regulating the expression of negative regulator TGFβ-1. This may be one of the mechanisms of anti-angiogenesis of Genistein.

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