Vascular responses to compound 48/80 in rat mesenteric vascular beds

2016 ◽  
Vol 94 (6) ◽  
pp. 620-626 ◽  
Author(s):  
Honghua Jin ◽  
Zhen Li ◽  
Shingo Takatori ◽  
Toshihiro Koyama ◽  
Xin Jin ◽  
...  

A further investigation was performed on the vascular effect of endogenous histamine using the histamine releaser, compound 48/80, in rat mesenteric vascular beds with active tone. In preparations with intact endothelium, low concentrations of compound 48/80 (1.53 × 10−5 – 3 × 1.53 × 10−5 mg/mL) perfusion for 1 min only induced a small vasodilation. High concentrations of compound 48/80 (1.53 × 10−4 – 3 × 1.53 × 10−2 mg/mL) induced a biphasic vascular responses, an initial vasoconstriction followed a subsequent long-lasting vasodilation. The vasodilation induced by low concentrations of compound 48/80 and the vasoconstriction induced by high concentration of compound 48/80 was inhibited by olopatadine. However, cimetidine did not affect the responses induced by compound 48/80. Endothelium removal enlarged the compound 48/80-induced phase-2 vasoconstriction, while it attenuated the phase-3 vasodilation. Additionally, indomethacin and seratrodast significantly inhibited vasoconstriction but it did not affect the long-lasting vasodilation induced by high concentrations of compound 48/80. Ruthenium red inhibited the vasodilation induced by low concentrations and high concentrations of compound 48/80. These results suggest that the vasoconstriction induce by high concentrations of compound 48/80 is mediated by endogenous histamine released from mast cells. It is also suggested that thromboxane A2 released from mast cells is related to the vasoconstriction.

2022 ◽  
Vol 12 ◽  
Author(s):  
Donghao Gan ◽  
Wenxiang Cheng ◽  
Liqing Ke ◽  
Antonia RuJia Sun ◽  
Qingyun Jia ◽  
...  

Pirfenidone (PFD), a synthetic arsenic compound, has been found to inhibit angiogenesis at high concentrations. However, the biphasic effects of different PFD concentrations on angiogenesis have not yet been elucidated, and the present study used an in vitro model to explore the mechanisms underlying this biphasic response. The effect of PFD on the initial angiogenesis of vascular endothelial cells was investigated through a Matrigel tube formation assay, and the impact of PFD on endothelial cell migration was evaluated through scratch and transwell migration experiments. Moreover, the expression of key migration cytokines, matrix metalloproteinase (MMP)-2 and MMP-9, was examined. Finally, the biphasic mechanism of PFD on angiogenesis was explored through cell signaling and apoptosis analyses. The results showed that 10–100 μM PFD has a significant and dose-dependent inhibitory effect on tube formation and migration, while 10 nM–1 μM PFD significantly promoted tube formation and migration, with 100 nM PFD having the strongest effect. Additionally, we found that a high concentration of PFD could significantly inhibit MMP-2 and MMP-9 expression, while low concentrations of PFD significantly promoted their expression. Finally, we found that high concentrations of PFD inhibited EA.hy926 cell tube formation by promoting apoptosis, while low concentrations of PFD promoted tube formation by increasing MMP-2 and MMP-9 protein expression predominantly via the EGFR/p-p38 pathway. Overall, PFD elicits a biphasic effect on angiogenesis through different mechanisms, could be used as a new potential drug for the treatment of vascular diseases.


Plant Disease ◽  
2020 ◽  
Vol 104 (2) ◽  
pp. 430-437
Author(s):  
Junye Jiang ◽  
Rudolph Fredua-Agyeman ◽  
Stephen E. Strelkov ◽  
Sheau-Fang Hwang

The planting of clubroot resistant (CR) canola (Brassica napus) is the most effective method to manage clubroot. Since 2013, many Plasmodiophora brassicae isolates capable of overcoming resistance have been detected, often in mixtures with avirulent isolates. To improve understanding of the effect of low concentrations of virulent isolates on host resistance, three CR canola cultivars (45H29, L135C, and L241C) were inoculated with pairs of isolates representing virulent/avirulent pathotypes (2*/2, 3*/3, and 5*/5) collected after or before the introduction of CR canola, respectively. Seven-day-old seedlings of each cultivar were incubated for 2 days in low concentrations (1 × 103 spores/ml) of the virulent isolates, followed by a second inoculation with a high concentration (1 × 107 spores/ml) of the avirulent isolates. Positive controls comprised seedlings inoculated with low concentrations of the virulent isolates followed by high concentrations of the virulent isolates (PC1) or only with high concentrations of virulent isolates (PC2). Negative controls comprised seedlings inoculated only with high concentrations of the avirulent isolates (NC1) or only with low concentrations of the virulent isolates (NC2). Clubroot severity was significantly higher in all nine experimental treatments (low virulent plus high avirulent) than in the negative control NC1 (high avirulent) but was lower in the experimental treatments than in the positive controls (PC1 and PC2). Low concentrations of virulent isolates alone (NC2) caused moderate clubroot. Disease severity correlated well with P. brassicae biomass in canola as determined by quantitative PCR analysis 28 to 35 days after inoculation. This study revealed that low concentrations of virulent isolates compromised canola resistance for infection by avirulent isolates.


2001 ◽  
Vol 280 (2) ◽  
pp. H767-H776 ◽  
Author(s):  
Tetsuyoshi Horiuchi ◽  
Hans H. Dietrich ◽  
Shinichiro Tsugane ◽  
Ralph G. Dacey

Effects of extraluminal UTP were studied and compared with vascular responses to ATP and its analogs in rat cerebral-penetrating arterioles. UTP, UDP, 2-methylthio-ATP, and α,β-methylene-ATP dilated arterioles at the lowest concentration and constricted them at high concentrations. Low concentrations of ATP dilated the vessels; high concentrations caused a biphasic response, with transient constriction followed by dilation. Endothelial impairment inhibited ATP- and UTP-mediated dilation and potentiated constriction to UTP but not to ATP. ATP- and 2-methylthio-ATP- but not UTP-mediated constrictions were inhibited by desensitization with 10−6M α,β-methylene-ATP or 3 × 10−6M pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS). PPADS at 10−4M abolished the UTP-mediated constriction and induced vasodilation in a dose-dependent manner but did not affect the dilation to ATP. These results suggest that in rat cerebral microvessels 1) ATP and 2-methylthio-ATP induce transient constriction via smooth muscle P2X1receptors in the cerebral arteriole, 2) UTP stimulates two different classes of P2Yreceptors, resulting in constriction (smooth muscle P2Y4) and dilation (possibly endothelial P2Y2), and 3) ATP and UTP produce dilation by stimulation of a single receptor (P2Y2).


2000 ◽  
Vol 6 (S2) ◽  
pp. 850-851
Author(s):  
Geoffrey Gobert ◽  
Ed Curren ◽  
Wade Welshons ◽  
Qing-yuan Sun ◽  
Heide Schatten

A highly significant correlation between reduced incidence of breast cancer in Asian countries and consumption of soy suggests that specific components in soy may have anticarcinogen activity. The soy ingredients genistein and daidzein have been found to inhibit induced breast tumors in animal and cell culture models. These isoflavones are known to be both agonists and antagonists of estrogen activity but only genistein is also a potent inhibitor of tyrosine kinases which are the primary intracellular signalling mechanisms associated with the regulation of cell proliferation.Genistein promotes cell proliferation in breast cancer cells at low concentrations in its function as estrogen agonist but inhibits cell proliferation at high concentrations (30 μM). In order to investigate the underlying mechanisms by which high concentration of genistein inhibit cell proliferation we treated MCF-7 cells with increasing concentrations of genistein and analyzed cells by immunofluorescence and transmission electron microscopy (TEM).


2016 ◽  
Vol 18 (1) ◽  
pp. 214-222 ◽  

<p>Ultramafics represent magmatic or metamorphic rocks which are characterized by high concentrations of Mg, Fe, Ni, Cr and Co and low concentrations of Ca, and K. Serpentine soils are weathered products of a range of ultramafic rocks composed of ferromagnesian silicates. The aim of this study was to determine the content of heavy metals in some of serpentine soils of Kosovo and heavy metals uptake by entire associated flora. Furthermore, another objective of this study was finding out bioavailable Ca/Mg relationship, which is very important indicator for plants&rsquo; development. The sampling was conducted in June 2014. A total of three serpentine areas have been surveyed and 7 soil samples have been taken in various depths of soil profiles. Those samples were analyzed for total Ca, Cd, Co, Cr, Cu, Mn, Ni, Pb, Fe and Zn. Results showed that each site exhibited a high concentration of at least one metal. The maximum concentrations of metals in soils Dry Matter (DM) were 108.9 mg kg<sup>-1</sup> Cd, 95.8 mg kg<sup>-1</sup> Co, 1206 mg kg<sup>-1</sup> Cr, 24 mg kg<sup>-1</sup> Cu, 2570 mg kg<sup>-1</sup> Ni, 21.7 mg kg<sup>-1</sup> Pb, 39 mg kg<sup>-1</sup> Zn, and 51563 mg kg<sup>- </sup>Fe. The serpentine soils at all sites were characterized by elevated levels of heavy metals, which showed typical properties of ultramafic environments. Nickel Total at studied areas varied between 1543 and 2570 mg kg<sup>-1</sup>, while the highest Ni concentration was found in aerial part of Alyssum markgrafii (4038 mgkg<sup>-1</sup>),</p> <div> <p>Based on our findings on the field we concluded that there is a close relationship between the quantity of Ni in soil and Ni uptake in plants.</p> </div> <p>&nbsp;</p>


1986 ◽  
Vol 251 (5) ◽  
pp. G602-G610 ◽  
Author(s):  
J. P. Dehaye ◽  
J. Winand ◽  
C. Damien ◽  
F. Gomez ◽  
P. Poloczek ◽  
...  

Helodermin is a new peptide isolated from the venom of Heloderma suspectum. Its effects on rat pancreatic acini were compared with those of secretin and vasoactive intestinal peptide (VIP). Four classes of receptors with decreasing affinity for secretin (S1, S2, S3, and S4) were first delineated. Occupancy of S1 and S2 by secretin was responsible for a biphasic adenosine 3',5'-cyclic monophosphate (cAMP) response. S3 was VIP preferring so that the VIP-induced increase in cAMP could be inhibited by VIP-(10 --28). S2 and S3 allowed cAMP elevation, protein phosphorylation, weak secretory effects, and potentiation of cholecystokinin octapeptide (CCK-8) when occupied by secretin and VIP, respectively. A more efficient exocytosis was observed with secretin interacting with low-affinity receptors S4. Helodermin increased cAMP levels 14-fold, this increase being inhibited by VIP-(10–28). Low concentrations of helodermin stimulated amylase secretion twofold and potentiated secretion by CCK-8. High concentrations of helodermin stimulated secretion another 2.6-fold. Helodermin bound to the four secretin receptors with a weak selectivity. At low concentration, helodermin stimulated cAMP elevation, protein phosphorylation, amylase release, and potentiation of CCK-8 through S3, whereas at high concentration it stimulated secretion via S4.


2001 ◽  
Vol 15 (2) ◽  
pp. 47-55 ◽  
Author(s):  
Nadide Kazanci ◽  
Neslihan Toyran ◽  
Parvez I. Haris ◽  
Feride Severcan

Fourier Transform Infrared spectroscopic studies show that low concentrations of vitamin D2(1 and 3 mol %) does not induce significant change in the overall shape of the thermotropic profile of dipalmitoyl phosphatidylcholine (DPPC) membrane. In contrast, at higher concentrations of vitamin D2(9 and 12 mol %), the phase transition shifts to lower temperatures and a significant broadening in the phase transition curve is also observed. Low concentration of vitamin D2decreases the frequency of the CH2stretching mode, implying an ordering effect, whilst high concentration of vitamin D2disorders the system. Furthermore, at low and high concentrations, vitamin D2causes opposing effect on membrane dynamics. It decreases the bandwidth of the CH2stretching modes at low concentrations while increasing it at high concentrations. We have also observed different actions of vitamin D2at low and high concentrations in the deep interior and interfacial region of the membrane, by monitoring the frequency of the CH3stretching band and C=O stretching bands, respectively.


2020 ◽  
Vol 71 (1) ◽  
pp. 100-106
Author(s):  
Daniel Mitru ◽  
Gheorghe Nechifor ◽  
Stefania Gheorghe ◽  
Alina Roxana Banciu ◽  
Lucian Ionescu ◽  
...  

The widespread use of detergents has raised concern with regard to the environmental pollution caused by their active substances, which are biorefractory, toxic or persistent. Even though anionic and non-ionic surfactants often used in commercial detergents composition are reasonably degradable under aerobic conditions and not particularly toxic at low concentrations, high concentration of surfactants influenced the activated sludge activity and are harmful for the aquatic environment. In the literature, data on the biodegradability and/or ecotoxicity of a certain type of surfactant (anionic, nonionic, cationic) are usually presented. Our study aimed to assess the biodegradability of a mixture of two types of surfactants (anionic mixed with non-ionic) and also, effects caused by their presence of elevated concentrations to the activated sludge micro-organisms, within a batch experiment. We performed a biodegradability test (according Zahn-Wellens method) on 2 synthetic solutions with high concentrations of anionic surfactant �methyl dodecylbenzene sulfonate (15-25 mg/L) and non-ionic surfactant -4-nonylphenyl-polyethylene glycol (10 mg/L). The study established different percent of biodegradability (measured by COD decrease and surfactants removal) depending on initial concentrations of anionic and nonionic surfactants in the tested solutions. High surfactants concentrations modulated the activity and morphology of activated sludge, so its degradation efficiency of the organic substrate has decreased. Surfactant solutions resulting from biodegradability experiment have been tested for toxicity to planktonic crustaceans (Daphnia magna).


1980 ◽  
Vol 188 (3) ◽  
pp. 789-798 ◽  
Author(s):  
S Cockcroft ◽  
B D Gomperts

The concentration-dependence on exogenous ATP of activation and inhibition of mast-cell histamine secretion, phosphatidylinositol labelling and leakage of metabolites shows that all these functions are regulated by the free acid ATP4-. Maximal histamine secretion and phosphatidylinositol labelling occur with ATP4- at approx. 2 microM, but higher concentrations, which cause inhibition of secretion and phosphatidylinositol labelling, are required to maximize leakage of 32P-labelled metabolites. Both enhancement and inhibition of phosphatidylinositol labelling (due to low and high concentrations of ATP4- respectively) are rapid in onset; histamine secretion is characterized by a delay, especially at low concentrations of ATP4- (approx. 1 microM). Phosphatidylinositol labelling and histamine secretion are dependent on extracellular Ca2+. Metabolite leakage due to the presence of exogenous ATP4- is slow and does not require Ca2+. Of 18 analogues of ATP that were tested, only four were agonists for secretion, and only these four permitted leakage of 32P-labelled metabolites. It is argued that activation and inhibition of histamine secretion, phosphatidylinositol labelling and metabolite leakage are all initiated by ATP4- acting at the same receptor. For mast cells stimulated with ATP4- enhancement of phosphatidylinositol metabolism is not sufficient by itself to cause Ca2+-dependent secretion.


1997 ◽  
Vol 328 (2) ◽  
pp. 371-375 ◽  
Author(s):  
Georges HILAL ◽  
David CLAVEAU ◽  
Marie LECLERC ◽  
Michèle G. BRUNETTE

We previously reported that parathyroid hormone and calcitonin increase Ca2+ uptake by purified distal luminal membranes. This effect is mimicked by high concentrations of cAMP. However, both hormones stimulate adenylate cyclase and phospholipase C. The purpose of the present study was to investigate the role of the phospholipase C pathway in the hormone action, and the interrelationship between the two messengers. Distal tubules from rabbit kidneys were incubated with dibutyryl cAMP (dbcAMP) or PMA, or both, and Ca2+ uptake by purified luminal membranes was measured by the rapid filtration technique. Incubation of the distal tubules with 1 mM dbcAMP significantly increased Ca2+ transport by the luminal membranes. A dose-response curve showed a half-maximal stimulation with 0.82 mM dbcAMP. In contrast, treatment of the tubules with 10 nM, 100 nM or 1 μM PMA did not influence Ca2+ uptake by these membranes. However, the addition of 100 nM PMA to low concentrations of dbcAMP strongly increased this uptake. The presence of cAMP or protein kinase C inhibitors prevented the effects of either a high concentration of dbcAMP alone or a low concentration of dbcAMP combined with 100 nM PMA. Our laboratory has already reported that Ca2+ uptake by the distal luminal membranes displays two-component kinetics. dbcAMP increased the Vmax of the low-affinity component, whereas a combination of the two messengers stimulated the Vmax of both the low- and high-affinity components. From these results, we conclude that: (1) in the distal tubule cells, activation of both protein kinases A and C is necessary for the stimulation of Ca2+ transport by the luminal membrane; (2) the combined effect of protein kinases A and C involves both components of the Ca2+-transport kinetics.


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