scholarly journals Pharmacological Manipulations of ATP-Dependent Potassium Channels and Adenosine A1 Receptors do not Impact Hippocampal Ischemic Preconditioning in Vivo: Evidence in a Highly Quantitative Gerbil Model

2004 ◽  
Vol 24 (5) ◽  
pp. 556-563 ◽  
Author(s):  
Takatoshi Sorimachi ◽  
Thaddeus S. Nowak
Keyword(s):  
Ischemic Preconditioning ◽  
Intraperitoneal Injection ◽  
Adenosine A1 ◽  
Neuron Damage ◽  
A1 Receptor ◽  
Ischemic Depolarization ◽  
Pharmacological Manipulations ◽  
Dose Dependent ◽  
Ischemic Neuronal Injury

Ischemic preconditioning models have been characterized in brain, heart, and other tissues, and previous pharmacologic studies have suggested an involvement of adenosine and ATP dependent potassium (KATP) channels in such tolerance phenomena. This question was reexamined in a reproducible gerbil model in which the duration of ischemic depolarization defined the severity of preconditioning and test insults. Agents studied were glibenclamide, a blocker of KATP channels; 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptor antagonist; and N6-cyclopentyladenosine (CPA), an A1 agonist. Intraventricular glibenclamide injections aggravated neuron damage after brief priming insults, in parallel with a dose-dependent prolongation of ischemic depolarization. However, the depolarization thresholds for ischemic neuronal injury were identical in vehicle- and glibenclamide-treated animals, and glibenclamide did not affect preconditioning when equivalent insult severity was maintained during priming insults. Neither DPCPX nor CPA had any effect on the onset or duration of depolarization after intraperitoneal injection in this model, and neither drug affected neuron damage. In the case of CPA, it was necessary to maintain temperature for 4 to 6 hours of recirculation to avoid significant confounding hypothermia. These results fail to support a direct involvement of A1 receptors or KATP channels during early stages in the development of ischemic tolerance in vivo, and emphasize the need for robust, well-controlled, and quantitative models in such studies.

The in vivo respiratory phenotype of the adenosine A1 receptor knockout mouse

2016 ◽  
Vol 222 ◽  
pp. 16-28 ◽  
Author(s):  
Dirk Heitzmann ◽  
Philipp Buehler ◽  
Frank Schweda ◽  
Michael Georgieff ◽  
Richard Warth ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Adenosine A1 Receptor ◽  
Receptor Knockout Mouse ◽  
Adenosine A1 ◽  
A1 Receptor

Ischemic preconditioning protects against infarction in rat heart

1992 ◽  
Vol 263 (4) ◽  
pp. H1107-H1112 ◽  
Author(s):  
Y. Liu ◽  
J. M. Downey
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Rat Heart ◽  
Channel Blocker ◽  
Isolated Rat Heart ◽  
Control Group ◽  
Risk Zone ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Coronary Ischemia

We examined the anti-infarct effect of ischemic preconditioning in the rat heart. All hearts were subjected to 30 min of regional coronary ischemia and 2 h of reperfusion. Infarct size was determined by tetrazolium. The control group had an average infarct size of 31% of the risk zone. Three 5-min cycles of preconditioning ischemia limited the infarct size to 3.7%. Neither the adenosine receptor blocker PD 115,199 nor the ATP-sensitive potassium channel blocker, glibenclamide, could block this protection. Intracoronary adenosine A1-receptor agonist 2-chloro-N6-cyclopentyladenosine offered a significant anti-infarct protection to the isolated rat heart, however. Although one 5-min cycle of preconditioning did not protect the rat heart from infarction (31% infarction in risk zone), it did attenuate arrhythmias. We conclude that 1) the rat heart can be preconditioned, which argues against mitochondrial adenosinetriphosphatase being the mechanism of preconditioning; 2) the threshold for preconditioning is higher in rat than rabbit or dog; 3) a role for adenosine in preconditioning was only partially supported; and 4) a role for ATP-sensitive potassium channels was not supported.

The p38 MAPK Inhibitor SB203580 Blocks Adenosine A1 Receptor-Induced Attenuation of In Vivo Myocardial Stunning

2004 ◽  
Vol 18 (6) ◽  
pp. 433-440 ◽  
Author(s):  
Yukihiro Yoshimura ◽  
Gentian Kristo ◽  
Byron J. Keith ◽  
Salik A. Jahania ◽  
Robert M. Mentzer ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Myocardial Stunning ◽  
Adenosine A1 Receptor ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
P38 Mapk Inhibitor ◽  
Mapk Inhibitor

scholarly journals Cordycepin Modulate Body Weight by Reducing Prolactin via an Adenosine A1 Receptor

2018 ◽  
Author(s):  
Yuan Li ◽  
Yan Li ◽  
Xueyan Wang ◽  
Hongyue Xu ◽  
Chao Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Prolactin Secretion ◽  
Adenosine A1 Receptor ◽  
Gh3 Cells ◽  
Serum Prolactin ◽  
Prolactin Release ◽  
Adenosine A1 ◽  
A1 Receptor

Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A1 receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A1 receptor.

Cordycepin Modulates Body Weight by Reducing Prolactin Via an Adenosine A1 Receptor

2018 ◽  
Vol 24 (27) ◽  
pp. 3240-3249 ◽  
Author(s):  
Yuan Li ◽  
Yan Li ◽  
Xueyan Wang ◽  
Hongyue Xu ◽  
Chao Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Lipid ◽  
Adenosine A1 Receptor ◽  
Gh3 Cells ◽  
Serum Prolactin ◽  
Lipid Levels ◽  
Adenosine A1 ◽  
A1 Receptor

Background: Cordycepin is an extract from the insect fungus Cordyceps. militaris with various biological function. In previous studies, cordycepin has demonstrated an excellent anti-obesity effect, but the mechanism is unclear. It was also demonstrated that prolactin played an important role in body weight regulation and hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin. Methods: In Vivo, the obese rat model was induced by high fat diet for five weeks, and the serum and liver lipid levels coupled with the serum prolactin levels were reduced following cordycepin treatment (P<0.01). Results: The results suggested that cordycepin is a potential drug that lowers blood and liver lipid levels and reduces body weight related to prolactin. Cordycepin also protects adipocytes from enlargement and hepatocytes from lipotoxicity-induced inflammation. In vitro, cordycepin inhibited prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, and the inhibition effect was blocked by an antagonist of adenosine receptor A1 DPDPX, demonstrating that cordycepin may work as an adenosine agonist. Additionally, cordycepin inhibited the ERK/AKT/PI3K pathway in GH3 cells. At the same time, cordycepin blocked prolactininduced upregulation of lipogenesis genes PRLR, and phosphorylation of JAK2 in 3T3-L1 cells. In an in vivo study, cordycepin downregulated the expression of prolactin receptor (PRLR) but not the phosphorylation of JAK2. Conclusion: Thus, it was proved that cordycepin modulates body weight by reducing prolactin release via an adenosine A1 receptor.

Adenosine attenuation of catecholamine-enhanced contractility of rat heart in vivo

1991 ◽  
Vol 260 (5) ◽  
pp. H1635-H1639 ◽  
Author(s):  
F. D. Romano ◽  
T. S. Naimi ◽  
J. G. Dobson
Keyword(s):  
Rat Heart ◽  
Receptor Agonist ◽  
Jugular Vein ◽  
Cardiac Contractility ◽  
Physiological Role ◽  
Inotropic Effects ◽  
Adenosine A1 ◽  
Positive Inotropic Effects ◽  
A1 Receptor

The antiadrenergic action of adenosine was examined in open- and closed-chest preparations of anesthetized rats. The positive inotropic effects of a jugular vein infusion of either isoproterenol or epinephrine were attenuated by phenylisopropyladenosine, an adenosine A1-receptor agonist. 1,3-Dipropyl,8-cyclopentylxanthine, a specific A1-receptor antagonist, inhibited the action of phenylisopropyladenosine. The results indicate that adenosine receptor-mediated mechanisms are functional in the blood-perfused rodent heart and support the possibility of a physiological role for adenosine in modulating cardiac contractility.

Protein phosphatase inhibition and in vivo hepatotoxicity of microcystins

1993 ◽  
Vol 265 (2) ◽  
pp. G224-G230 ◽  
Author(s):  
M. T. Runnegar ◽  
S. Kong ◽  
N. Berndt
Keyword(s):  
Protein Phosphatase ◽  
Intraperitoneal Injection ◽  
Significant Inhibition ◽  
Protein Phosphatase 1 ◽  
Liver Protein ◽  
Protein Phosphatase Inhibition ◽  
Clinical Changes ◽  
Dose Dependent ◽  
Lethal Doses

Administration of microcystin (MCYST)-YM or -LR (peptide hepatotoxins produced by the cyanobacterium Microcystis aeruginosa) to mice resulted in the inhibition of liver protein phosphatase 1 and 2A activity. In all cases significant inhibition preceded or accompanied clinical changes due to MCYST intoxication. Fifteen minutes after intraperitoneal injection of lethal doses of MCYST-YM protein phosphatase activity was already decreased to 44% of controls, and by 60 min was further decreased to 22% of controls. The inhibition was dose dependent: intraperitoneal injection with 84 nmol/kg of MCYST-YM and 48 nmol/kg of MCYST-LR were the minimum doses required for significant inhibition at 60 min. Pretreatment of mice with 200 mumol/kg of rifamycin prevented the inhibition of liver protein phosphatase. The inhibition was tissue specific, with none detected in the kidneys, an organ that, unlike the liver, does not accumulate MCYST. In contrast to MCYST intoxication, lethal doses of phalloidin, a peptide hepatotoxin that produces clinical and pathological changes similar to MCYST, did not cause any inhibition of protein phosphatases.

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