Cardiolipins are ‘in vitro’ inhibitors of rat brain A probable mechanism of action (Na+ + K+)-dependent ATPase

1981 ◽  
Vol 642 (1) ◽  
pp. 96-105 ◽  
Author(s):  
Efrain Toro-Goyco ◽  
Matilde B. Rodriguez ◽  
Alan M. Preston ◽  
Arthur F. Rosenthal
Author(s):  
B. Jassal ◽  
B. Kumar ◽  
V. Bajaj ◽  
R. Walia

<strong>Background:</strong>Terminalia arjuna is being used in various cardiovascular diseases as cardiotonic, diuretic&amp;in hypercholesterolemia. Studies conflict each other for its mechanism of action. This study aims to investigate effect of 90% alcoholic extract of Terminalia arjuna on in vitro isolated rabbit's heart&amp;to find its probable mechanism of action.<p><strong>Objective:</strong> To study the preliminary pharmacological effects of 90% alcoholic extract of Terminalia arjuna in-vitro on isolated heart, coronary blood flow, and to study its probable mechanism of action.</p><p><strong>Material&amp;Methods:</strong> Effect of Terminalia arjuna was observed on heart rate, coronary blood flow, amplitude on in vitro isolated perfused rabbit's heart mounted on langendorff apparatus&amp;further cholinergic&amp;adrenergic blockers were used to study the mechanism of action. Six experiments were conducted for each parameter&amp;data was analysed using Student's t test.</p><p><strong>Results:</strong> Terminalia arjuna causes mean percentage decrease of 7.26%, 9.31%&amp;20.51% in heart rate, decrease of 10.34%, 16.64%, 20.51% in coronary blood flow&amp;decrease of 15.11%, 12.61%, 11.65% in amplitude at 25μg, 50μg&amp;100μg doses respectively. The decrease in heart rate, coronary blood flow&amp;amplitude persists even after cholinergic&amp;adrenergic blockers suggesting that cholinergic&amp;adrenergic receptors are not involved in mechanism of Terminalia arjuna.</p><p><strong>Conclusion:</strong> Terminalia arjuna cardiodepressant effect does not involve cholinergic&amp;adrenergic receptors.</p>


1984 ◽  
Vol 66 (4) ◽  
pp. 415-420 ◽  
Author(s):  
H. W. M. Seda ◽  
C. D. Gove ◽  
R. D. Hughes ◽  
Roger Williams

1. Sera from patients with fulminant hepatic failure (FHF) has previously been shown to contain substance(s) which inhibit leucocyte ouabain-sensitive sodium efflux and rat brain Na+,K+-dependent ATPase in vitro. Similar effects in the patients could be an important mechanism in the development of encephalopathy and cerebral oedema. 2. In previous studies, bilirubin, free fatty acids and mercaptans have been shown to inhibit Na+,K+-ATPase in vitro. The present report is concerned with the effects of a number of other potentially toxic substances present in the serum of patients with FHF. 3. Chenodeoxycholic acid, p-hydroxyphenyllactic acid, p-hydroxyphenylpyruvic acid and endotoxin caused 30–45% inhibition of partially purified rat brain Na+,K+-ATPase at concentrations known to occur in the serum of patients with FHF. At low concentrations the inhibitory effects of these substances were additive, but at higher concentrations a maximum level of inhibition was reached. 4. These further substances are likely, therefore, to be of importance in the disturbances of brain function found in FHF.


2011 ◽  
Vol 46 (9) ◽  
pp. 3616-3622 ◽  
Author(s):  
Tassiele A. Heinrich ◽  
Gustavo Von Poelhsitz ◽  
Rosana I. Reis ◽  
Eduardo E. Castellano ◽  
Ademir Neves ◽  
...  

1973 ◽  
Vol 29 (03) ◽  
pp. 694-700 ◽  
Author(s):  
Paul L. Rifkin ◽  
Marjorie B. Zucker

SummaryDipyridamole (Persantin) is reported to prolong platelet survival and inhibit embolism in patients with prosthetic heart valves, but its mechanism of action is unknown. Fifty jxM dipyridamole failed to reduce the high percentage of platelets retained when heparinized human blood was passed through a glass bead column, but prolonged the inhibition of retention caused by disturbing blood in vitro. Possibly the prostheses act like disturbance. Although RA 233 was as effective as dipyridamole in inhibiting the return of retention, it was less effective in preventing the uptake of adenosine into erythrocytes, and more active in inhibiting ADP-induced aggregation and release. Thus there is no simple relation between these drug effects.


1996 ◽  
Vol 40 (9) ◽  
pp. 2094-2098 ◽  
Author(s):  
B Pradines ◽  
F Ramiandrasoa ◽  
L K Basco ◽  
L Bricard ◽  
G Kunesch ◽  
...  

The activities of novel iron chelators, alone and in combination with chloroquine, quinine, or artemether, were evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum with a semimicroassay system. N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7) demonstrated the highest level of activity: 170 nM against a chloroquine-susceptible clone and 1 microM against a chloroquine-resistant clone (50% inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on the activities of chloroquine, quinine, and artemether against either clone, and compound 8 did not enhance the schizontocidal action of either chloroquine or quinine against the chloroquine-resistant clone. The incubation of compound 7 with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound 7, while no effect was observed with incubation of compound 7 with CuSO4 and ZnSO4. These results suggest that iron deprivation may be the main mechanism of action of compound 7 against the malarial parasites. Chelator compounds 7 and 8 primarily affected trophozoite stages, probably by influencing the activity of ribonucleotide reductase, and thus inhibiting DNA synthesis.


2002 ◽  
Vol 22 (12) ◽  
pp. 1476-1489 ◽  
Author(s):  
Nancy F. Cruz ◽  
Gerald A. Dienel

The concentration of glycogen, the major brain energy reserve localized mainly in astrocytes, is generally reported as about 2 or 3 μmol/g, but sometimes as high as 3.9 to 8 μmol/g, in normal rat brain. The authors found high but very different glycogen levels in two recent studies in which glycogen was determined by the routine amyloglucosidase procedure in 0.03N HCl digests either of frozen powders (4.8 to 6 μmol/g) or of ethanol-insoluble fractions (8 to 12 μmol/g). To evaluate the basis for these discrepant results, glycogen was assayed in parallel extracts of the same samples. Glycogen levels in ethanol extracts were twice those in 0.03N HCl digests, suggesting incomplete enzyme inactivation even with very careful thawing. The very high glycogen levels were biologically active and responsive to physiologic and pharmacological challenge. Glycogen levels fell after brief sensory stimulation, and metabolic labeling indicated its turnover under resting conditions. About 95% of the glycogen was degraded under in vitro ischemic conditions, and its “carbon equivalents” recovered mainly as glc, glc-P, and lactate. Resting glycogen stores were reduced by about 50% by chronic inhibition of nitric oxide synthase. Because neurotransmitters are known to stimulate glycogenolysis, stress or sensory activation due to animal handling and tissue-sampling procedures may stimulate glycogenolysis during an experiment, and glycogen lability during tissue sampling and extraction can further reduce glycogen levels. The very high glycogen levels in normal rat brain suggest an unrecognized role for astrocytic energy metabolism during brain activation.


Peptides ◽  
1986 ◽  
Vol 7 (3) ◽  
pp. 425-429 ◽  
Author(s):  
Jeroen A.D.M. Tonnaer ◽  
Marianna Van Vugt ◽  
Joop S. De Graaf

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