Role of ET(A) and ET(B) receptors in endothelin-1-induced adrenal catecholamine secretion in vivo

1997 ◽  
Vol 272 (4) ◽  
pp. R1290-R1297 ◽  
Author(s):  
N. Yamaguchi
Keyword(s):  
High Performance ◽  
Low Dose ◽  
Dose Range ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Experimental Conditions ◽  
Chromatography Method ◽  
Liquid Chromatography Method

The present study was designed to test whether endothelin (ET) A and/or B receptors in the adrenal medulla are functionally involved in ET-1-induced catecholamine (CA) release in anesthetized dogs. ET-1 was locally infused into the gland via the left adrenolumbar artery. Plasma CA in adrenal venous and aortic blood was determined by a high-performance liquid chromatography method. In the control group, the local infusion of ET-1 (0.5 microg, 0.4 microM) resulted in a significant increase in CA output. In the presence of a low dose of BQ-123 (5 microg, 16.4 microM), the ET-1-induced CA response was significantly attenuated by approximately 80%. With a high dose of BQ-123 (50 microg, 164 microM), the CA response was further blocked by approximately 95%. This inhibition was significantly greater than that obtained with the low dose of BQ-123. By contrast, a low dose of BQ-788 (5 microg, 15.1 microM) did not significantly affect the CA response. With a high dose of BQ-788 (50 microg, 151 microM), the CA response was only partially inhibited by approximately 70%. The results indicate that BQ-123 significantly inhibited ET-1-induced adrenal CA release in a dose-dependent manner. With the low doses, the CA response was markedly inhibited by BQ-123 but remained unchanged in the presence of BQ-788. Moreover, the high dose of BQ-123 virtually abolished the CA response, whereas BQ-788 failed to do so within the dose range tested. The present study suggests that the ET(A) receptor may play a predominant role in mediating the ET-1-induced CA secretion in the canine adrenal gland in vivo, although the possible involvement of the ET(B) receptor could not completely be excluded under the present experimental conditions.

Implication of L-type Ca2+ channels in noncholinergic adrenal catecholamine secretion by endothelin-1 in vivo

1995 ◽  
Vol 269 (2) ◽  
pp. R287-R293 ◽  
Author(s):  
N. Yamaguchi
Keyword(s):  
High Performance ◽  
Cholinergic Receptor ◽  
Secondary Response ◽  
Control Group ◽  
Rapid Decline ◽  
Chromatography Method ◽  
Endothelin 1 ◽  
Liquid Chromatography Method ◽  
Ca2 Channels

The aim of the present study was to investigate if either dihydropyridine-sensitive L-type Ca2+ channels or cholinergic receptor-mediated mechanisms are implicated in endothelin-1 (ET)-induced adrenal catecholamine (CA) secretion in anesthetized dogs. ET was locally administered to the left adrenal gland via the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography method. In the control group, local infusion (1 min, 0.5 ml/min) of ET (the fixed total dose of 0.5 microgram given to the gland or approximately 0.0197 microgram/kg of body weight) resulted in a sharp increase in the basal CA output, followed by a rapid decline, and a relatively slow secondary response lasted over a period of 15-30 min. In the second group treated with nifedipine (5 micrograms or approximately 0.207 microgram/kg) similarly administered 10 min before ET infusion, the ET-induced first steep increase in CA output was significantly attenuated by approximately 75% (P < 0.05, n = 6). In dogs similarly receiving either pentolinium (1 mg or approximately 0.041 mg/kg) or atropine (0.5 mg or approximately 0.018 mg/kg), the ET-induced CA response remained unchanged. The results indicate that ET-induced adrenal CA release was largely mediated by the activation of dihydropyridine-sensitive L-type Ca2+ channels. Furthermore, neither nicotinic nor muscarinic receptors were functionally implicated in the CA response to ET. The study suggests the existence of noncholinergic mechanisms involved in the secretory action of ET on the adrenal medulla in the dog in vivo.

Role of L-type Ca2+ channel in PACAP-induced adrenal catecholamine release in vivo

1997 ◽  
Vol 273 (4) ◽  
pp. R1339-R1345 ◽  
Author(s):  
Guoju Geng ◽  
Rania Gaspo ◽  
Fethi Trabelsi ◽  
Nobuharu Yamaguchi
Keyword(s):  
Adrenal Medulla ◽  
High Performance ◽  
Dependent Manner ◽  
Amino Acid Residues ◽  
Chromatography Method ◽  
Pituitary Adenylate Cyclase ◽  
Group A ◽  
Anesthetized Dogs ◽  
Liquid Chromatography Method

The aim of the present study was to investigate whether the dihydropyridine-sensitive L-type Ca2+ channel is operative in adrenal catecholamine (CA) secretion induced by a novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography method. All drugs tested were locally infused into the left adrenal gland via the left adrenolumbar artery. PACAP, with the isoform consisting of 27 (PACAP-27) and 38 (PACAP-38) amino acid residues, significantly increased CA output in a dose-dependent manner, with doses ranging from 5 to 500 ng and 7 to 700 ng, respectively. However, the amplitude of epinephrine response to PACAP-27 was three times greater than that obtained with PACAP-38 at the highest dose tested. In a separate group, a single dose of PACAP-27 (50 ng) induced highly reproducible CA responses when the same dose was repeated with an interval of 35 min. In dogs treated with nifedipine (50 μg), 5 min before the second administration of PACAP-27, the net CA response was significantly inhibited by ∼50% compared with that obtained in the presence of vehicle. A similar CA response to BAY K 8644 (5 μg) was completely abolished by the same dose of nifedipine. The present results indicate that both PACAP-27 and PACAP-38 have the direct local secretagogue effect on the adrenal medulla in vivo and that CA responses to PACAP-27 were greater than those observed with PACAP-38 at equivalent mole doses. The study suggests that the dihydropyridine-sensitive L-type Ca2+ channel is functionally involved in PACAP-induced adrenal CA secretion in the canine adrenal medulla in vivo.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

Characterization by HPLC of p-Hydroxybenzyl Alcohol Biotransformation to Gastrodin In Vivo

2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110350
Author(s):  
Lijun Cheng ◽  
Yang Deng
Keyword(s):  
Bioactive Compounds ◽  
High Performance ◽  
Array Detector ◽  
Gastrodia Elata ◽  
Chromatography Method ◽  
Liquid Chromatography Method ◽  
First Time ◽  
Insight Into ◽  
Hydroxybenzyl Alcohol

Gastrodin (GAS) and its aglycone, p-hydroxybenzyl alcohol (HBA), are both bioactive compounds extracted from Gastrodia elata Blume (GEB). In the current Chinese pharmacopoeia, they are regarded as quality control markers for GEB. In this study, we developed a high-performance liquid chromatography method coupled with a diode array detector to quantify GAS and HBA concentrations in plasma following oral ingestion by rats. For the first time, GAS was detected in vivo after HBA administration. GAS and HBA both had similar pharmacological effects, but the influence of the glucose moiety resulted in different pharmacokinetic characteristics. In this study, the effects of GAS and HBA at different administration durations were investigated in zebrafish larvae. These compounds were found to induce a sedative effect but had different onset times. In conclusion, a biotransformation of HBA to GAS could be observed in the rats. This may be a new insight into the pharmacokinetic characteristics of these bioactive compounds and also relates to the different ways in which they take effect.

Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning

2004 ◽  
Vol 287 (6) ◽  
pp. H2746-H2753 ◽  
Author(s):  
Gentian Kristo ◽  
Yukihiro Yoshimura ◽  
Byron J. Keith ◽  
Randy M. Stevens ◽  
Salik A. Jahania ◽  
...  
Keyword(s):  
Myocardial Stunning ◽  
Receptor Agonist ◽  
Low Dose ◽  
Coronary Artery Occlusion ◽  
Receptor Activation ◽  
Artery Occlusion ◽  
Control Group ◽  
High Dose ◽  
Stroke Work

The purpose of this study was to determine whether the adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning. Regional stunning was produced by 15 min of coronary artery occlusion and 3 h of reperfusion (RP) in anesthetized open-chest pigs. In acute protection studies, animals were pretreated with saline, low-dose AMP-579 (15 μg/kg iv bolus 10 min before ischemia), or high-dose AMP-579 (50 μg/kg iv at 14 μg/kg bolus + 1.2 μg·kg−1·min−1 for 30 min before coronary occlusion). The delayed preconditioning effects of AMP-579 were evaluated 24 h after administration of saline vehicle or high-dose AMP-579 (50 μg/kg iv). Load-insensitive contractility was assessed by measuring regional preload recruitable stroke work (PRSW) and PRSW area. Acute preconditioning with AMP-579 dose dependently improved regional PRSW: 129 ± 5 and 100 ± 2% in high- and low-dose AMP-579 groups, respectively, and 78 ± 5% in the control group at 3 h of RP. Administration of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.7 mg/kg) blocked the acute protective effect of high-dose AMP-579, indicating that these effects are mediated through A1 receptor activation. Delayed preconditioning with AMP-579 significantly increased recovery of PRSW area: 64 ± 5 vs. 33 ± 5% in control at 3 h of RP. In isolated perfused rat heart studies, kinetics of the onset and washout of AMP-579 A1 and A2a receptor-mediated effects were distinct compared with those of other adenosine receptor agonists. The unique nature of the adenosine agonist AMP-579 may play a role in its ability to induce delayed preconditioning against in vivo myocardial stunning.

scholarly journals Sub-Chronic Toxicity Study of Hydroethanolic Leaf Extract of Telfairia Occidentalis Hook. F. (Cucurbitaceae) in Rats

2017 ◽  
Author(s):  
Abidemi J. Akindele ◽  
Joy A. Oladimeji-Salami ◽  
Ramon A. Oyetola ◽  
Daniel D. Osiagwu
Keyword(s):  
Leaf Extract ◽  
Chronic Toxicity ◽  
Biochemical Analysis ◽  
Low Dose ◽  
Oral Exposure ◽  
Control Group ◽  
High Dose ◽  
Telfairia Occidentalis ◽  
The Brain

Background: The leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria because of the numerous nutritional and medicinal attributes ascribed to it. The sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis (TO) was investigated in this study. Methods: Rats in different groups were separately administered 80, 400 and 2000 mg/kg TO p.o. for 60 days. Animals were sacrificed and blood samples collected for haematological and biochemical analysis. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: Results showed no significant changes in the weight of vital organs except in respect of the testes of the group treated with 2000 mg/kg extract which showed a significant (p&lt;0.05) reduction in weight compared to the control group. There was a significant (p&lt;0.01) increase in sperm motility and count of the group administered 80 mg/kg extract and a significant (p&lt;0.001) reduction was observed at 2000 mg/kg. There were significant increases in the level of Hb and PCV at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, a significant decrease in AST and ALT levels at doses of 400 and 2000 mg/kg relative to control was observed. A significant reduction (p&lt;0.05) in the level of total cholesterol (400 mg/kg) and increase (p&lt;0.05) in level of HDL (80-2000 mg/kg) compared to control was observed. There was also significant (p&lt;0.05) increase in the level of MDA and significant (p&lt;0.05) decrease in SOD level in the testes at 2000 mg/kg. Histopathological assessment of the testes revealed abnormality at this dose. These effects were reversed after 30 days of cessation of administration of TO. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposure, with potential to elicit anti-anaemic effect, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low dose, the extract could be harmful to the testes on prolonged oral exposure at high dose.

scholarly journals Development and Validation of Rapid and Sensitive HPLC Method for the Determination of Methotrexate in Human Serum

2010 ◽  
Vol 2 (1) ◽  
pp. 8-13 ◽  
Author(s):  
M Nagulu ◽  
V Uday Kiran ◽  
Y Narsimha Reddy ◽  
D Rama Krishna
Keyword(s):  
High Performance ◽  
Internal Standard ◽  
Hplc Method ◽  
High Dose ◽  
Chromatography Method ◽  
Quantitation Limit ◽  
High Doses ◽  
Liquid Chromatography Method ◽  
Development And Validation

Methotrexate competitively inhibits dihydrofolic acid reductase and thereby inhibits DNA synthesis and cellular replication.This study describes a simple and fast high-performance liquid chromatography method for the determination of methotrexate [MTX] in serum.samples were collected from adult cancer patients receiving high dose MTX at Mahathma Gandhi Memorial hospital (Warangal,AP.India) at various time intervals after the end of each infusion. Serum was deproteinized with trichloroacetic acid and the supernatant was injected into a 250×4.6 mm octadecylsilane column. Mobile phase was made of TRIS-phosphate buffer (pH 5.7): methanol: acetonitrile (70:20:10) with a flow rate of 1ml/min. Ultraviolet detection was done at 313 nm and at ambient temperature. Para aminoacetophenone was used as internal standard. Methotrexate and internal standard retention times were 4.6 and 9.5 minutes, respectively. Results showed that reproducibility (precision) of method within a day was 2.6 to 6 percent and between days was 5.5 to 9.5 percent. The recovery of the method was between 61.5 and 72.7 percent. The quantitation limit of the method for methotrexate was 0.1μM. This method is suitable for quantitation of methotrexate after infusion of high doses of this drug and has good accuracy, precision and quantitation limit. Key Words: Methotrexate; HPLC; Serum Concentration. DOI: 10.3329/sjps.v2i1.1693Stamford Journal of Pharmaceutical Sciences Vol.2(1) 2009: 8-13

In Vivo Anti-Hypoxia and Anti-Fatigue Activities of Flavonoids from Bark of Eucommia ulmoides

2014 ◽  
Vol 675-677 ◽  
pp. 1608-1611 ◽  
Author(s):  
Jin Yang Lin ◽  
Zhuo Ying Zhang
Keyword(s):  
Low Dose ◽  
Forced Swimming Test ◽  
Saline Solution ◽  
Liver Glycogen ◽  
Control Group ◽  
High Dose ◽  
Eucommia Ulmoides ◽  
Swimming Time ◽  
Swimming Test

The present study was carried out to investigate anti-hypoxia and anti-fatigue activities of flavonoids from bark of Eucommia ulmoides (FEU) in mice. The animal were divided into four groups: control (C) group, low-dose FEU treated (LF) group, intermediate dose FEU treated (IF) group and high-dose FEU treated (HF) group. The treated groups received FEU (5, 15, 45mg/kg), while the control group received saline solution for 28 days. After 28 days, anti-hypoxia activity of FEU was assessed by the normobarie hypoxia test and anti-fatigue activity of FEU was assessed by the forced swimming test. The data showed that FEU could prolong survival time of oxygen deprivation and exhaustive swimming time by reducing BLA and BUN levels and increasing liver glycogen and muscle glycogen contents. Therefore, FEU had anti-hypoxia and anti-fatigue activities.

scholarly journals Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 681 ◽  
Author(s):  
Renuka V. Iyer ◽  
Orla Maguire ◽  
Minhyung Kim ◽  
Leslie I. Curtin ◽  
Sandra Sexton ◽  
...  
Keyword(s):  
T Cells ◽  
Low Dose ◽  
Growth Delay ◽  
High Dose ◽  
Dependent Manner ◽  
Sorafenib Treatment ◽  
Baseline Activity ◽  
Dose Dependent

The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models. In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation. In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials.

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