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Biomedical subjects

N P Larionov

Publications and source records attributed to N P Larionov.

At least 19 recordsLinked to original sources
PubMed2002

Adaptation to heat limits stress-induced activation of caspases in the thymus.

We demonstrated selective activation of caspases in the thymus during heat shock, i.e. primary activation of initiator caspase 9 (but not caspase 8) and effector caspase 3 (but not caspase 6). Preadaptation to heat improved animal survival after heat shock and reduced heat shock-induced activation of both initiator and effector caspases. Hence, adaptation to heat produced an antiapoptotic effect, which was not selective towards receptor-dependent or mitochondrial pathway of the caspase cascade activation.

Adaptation, Physiological↗
PubMed2000

Cross-talk between nitric oxide and HSP70 in the antihypotensive effect of adaptation to heat.

In this work, we evaluated the effect of adaptation to heat on the fall of blood pressure (BP) induced by heat shock (HS) and the interrelation between nitric oxide (NO) and heat shock protein, HSP70. Experiments were carried out on Wistar rats. It was shown that HS resulted in a generalized and transient increase in NO production (the electron paramagnetic resonance method) and a fall of BP from 113+/-3 to 88+/-1 mm Hg (p<0.05). Adaptation to heat itself did not affect BP, but completely prevented the NO overproduction and hypotension induced by HS. The adaptation simultaneously increased the brain NO-synthase content and induced HSP70 synthesis (the Western blot analysis) in various organs. Both the antihypotensive effects of adaptation and HSP70 accumulation were completely prevented by L-NNA, an inhibitor of NO synthesis, or quercetin, an inhibitor of HSP70 synthesis. The data suggest that adaptation to heat stimulates NO synthesis and NO activates synthesis of HSP70. HSP70, which hampers NO overproduction, thus restricts the BP fall induced by heat shock.

Adaptation, Physiological↗
PubMed1996

Is HSP70 involved in nitric oxide-induced protection of the heart?

It is known that HSP70 plays an important role in the antiischaemic effect of adaptation to stress. The aim of our study was to verify the hypothesis that nitric oxide (NO) may contribute to the activation of HSP70 synthesis and to enhance thereby the resistance of organism to the ischaemic and reperfusion damages. We observed that heat shock potentiated NO production in the heart. NO formation was completely blocked by the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA). L-NNA also significantly attenuated the heat shock-induced accumulation of HSP70 (by 45% in heart). Both heat shock and NO donor induced time- and concentration-dependent HSP70 synthesis in the culture of human hepatoblastoma cells Hep G2. Prior injection of NO donor (30-100 mg per rat) exerted a dose-dependent protective effect on the isolated heart in ischaemia and reperfusion within 24 hours. We suggest that NO is involved in the activation of HSP70 synthesis which can play an important role in the delayed protective effect of NO donors.

Animals↗
PubMed1990

[Interaction of calcium agonists and antagonists with Ca-binding proteins and their effect on cyclic nucleotide phosphodiesterase].

The effects of Ca2+ antagonists (nicardipine, felodipine, nitrenedipine, isradipine, niphedipine, darodipine and riodipine) and Ca2+ agonists (BAY K8644 and CGP 28392), 1.4-dihydropyridine derivatives (1.2-DHP), on the calmodulin (CM)-dependent activation of cyclic nuxleotide phosphodiesterase (PDE) were studied. Both the blockers and activators of slow potential-dependent Ca2+ channels induced a un-competitive inhibition of the CM-dependent PDE activity. 1.4-DHP was found to replace the fluorescent probe, diS-C3-(5), from the Ca2(+)-dependent calmodulin-dye complex (K0.5 = 4-60 microM) but at concentrations below 100 microM had no effect on the Ca2(+)-dependent troponin C-dye complex. Darodipine (100 microM) did not interact with the proteins. The 1.4-DHP interaction with CM did not interfere with PDE activation. It is concluded that 1.4-DHP may affect Ca2+ dependent processes not only at the levels of activation or blocking of Ca2+ channels, but also through regulation of Ca2(+)-CM dependent enzymes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1990

[The effect of calmodulin inhibitors and the new cardiotonic drug DPI 201-106 on the formation of interprotein bonds in the cardiac troponin complex].

Using the binding of labeled [125I]troponin C (TnC) to troponin I (TnI) and troponin (TnT) immobilized on a polyvinylchloride matrix, the Ca-dependent formation of interprotein bonds in the cardiac troponin complex and the effects of various drugs on the above reaction were studied. It has been found that in the absence of Ca2+ the dissociation constant, Kd, for the TnC-TnI complex in equal to (2.5 +/- 1.03).10(-7) M. In the presence of Ca2+ the number of binding sites increases twofold; the Kd value for the bonds formed thereby is (1.74 +/- 0.18).10(-7) M. The complex is stable to the effect of 5 M urea. TnC binding to immobilized TnT is nonspecific and is completely abolished by an addition of 5 M urea. DPI 201-106 used at concentrations up to 10(-3) M does not affect the Ca-dependent binding of TnC to TnI; trifluoperazine inhibits this interaction by 60%, whereas substance 48/80 inhibits the reaction by 50% when used at a concentration of 210 micrograms/ml. It is supposed that the compounds interacting with TnC affect, primarily, the cation-binding properties of troponin. These compounds can also inhibit the formation of interprotein bonds but only when used at much higher concentrations.

Animals↗
PubMed1989

[Effect of calcium ions on the interaction of troponin C with rabbit skeletal muscle troponin I and troponin T immobilized on polyvinyl chloride].

Using a new methodological approach based on the binding of 125I-labeled troponin C to troponins I and T immobilized on polyvinylchloride, the Ca2+-dependent interaction of troponin components was investigated. In the absence of Ca2+, two types of sites of troponin C--troponin T interaction were revealed (Kd = 3.6.10(-8) M and 5.10(-7) M). It was found that Ca2+ induced the formation of a troponin I--troponin C complex which was resistant to 5 M urea (Kd = 4.10(-8) M). In the absence of Ca2+, the binary troponin T--troponin C complex also revealed two types of interaction sites (Kd = 7.1.10(-8) M and 2.10(-7) M); however, in the presence of Ca2+ only high affinity sites whose number increased almost 2-fold were revealed. The events that may take place in the whole troponin complex during Ca2+ binding by troponin C are discussed.

Animals↗
PubMed1989

[Prevention of adrenaline-induced arrhythmia by a calmodulin blocker, trifluoroperazine].

Adrenergic arrhythmias were induced in isolated rat hearts with epinephrine in a concentration of 5.10(-5) M in the perfusing solution. The rhythm disturbance was accompanied by a pronounced depression of contractility. It was found that the preliminary administration of the calmodulin blocker trifluoperazine (10(-6) M) decreased the duration of arrhythmias and the latency of their development, the contractility remaining at a higher level than in control. Verapamil administered into the perfusing solution did not significantly affect the latency of arrhythmias and reduced the duration of arrhythmias and the cardiotonic effect of epinephrine to a lesser extent than trifluoperazine. The mechanism is under discussion, by which the calmodulin blocker has a more pronounced cardioprotective antiarrhythmic effect than the Ca-channel blocker.

Animals↗
PubMed1988

[Prevention of ischemic and reperfusion arrhythmias using the calmodulin blocker trifluoperazine].

Models of ischemic and reperfusion arrhythmias were reproduced in isolated rat hearts by means of the ligation and subsequent reocclusion of the left descending coronary artery. The introduction of trifluoperazine (TFP, 10(-6) M) and verapamil (2.5 X 10(-8) M) into the perfusion medium produced a 20% depression of contractility in aerobic conditions; an additional depression of contractility at 20 min of ischemia and 10 min of reperfusion was 40 and 50%, respectively, for TFP and about the same for verapamil, as compared to the control. Antiarrhythmic effect of TFP was much higher, as compared to that of verapamil. The calmodulin blocker reduced fivefold total duration of arrhythmias, whereas the calcium-incorporation blocker only reduced it by 2.5 times. The antiarrhythmic effect of TFP was even more marked, as compared to verapamil, at reperfusion: TFP reduced total duration of ventricular tachycardias and ventricular fibrillations by 2 and 35 times, respectively, while verapamil had no effect on those types of arrhythmia. A possible mechanism of antiarrhythmic action of the calmodulin blocker TFP is discussed.

Animals↗
PubMed1986

[Role of calmodulin in the contractile function of the myocardium].

The effect of phenothiazines-trifluoroperazine frenolone, majeptile and aminazine on contractility of papillar muscle of Wistar male rats associated with short-term Ca-concentration increase up to 4 mM has been studied. There has been found the parameter-relaxation index-the change of which under the effect of phenothiazines (10(-5) M in all the cases) made use of significantly correlates with the constants, which reflect the similarity of given agents with calmodulin.

Animals↗
PubMed1986

[Protective effect of aminazine in ischemia and re-perfusion of an isolated heart].

The effect of cholorpromazine on the degree of reduction of the myocardial contractility during reperfusion of the isolated heart after 5 minutes total ischaemia of rats or after 40 minutes ligation of the left coronary artery of the guinea pigs has been studied. It has been shown that in both cases the preparation shows protective effect. In experiments on vesicles of sarcoplasmic reticulum (SR) of rat's skeletal muscles has been established that chlorpromazine prevents from calcium pump of SR dissociation caused by lipid peroxidation activity or by adding phospholipase A2 to SR fragments. It has been concluded that chlorpromazine protective effect depends on its membranostabilized action.

Animals↗
PubMed1984

The influence of phenothiazines on the sarcoplasmic reticulum Ca-ATPase from skeletal and cardiac muscles.

Phenothiazines--trifluoperazine, chloropromazine and ethmozine-- inhibit the sarcoplasmic reticulum Ca-ATPase from skeletal and cardiac muscles of the rabbit. The inhibition constants for both preparations are of the same order of magnitude. The experimental data suggest that the effect of phenothiazine on the sarcoplasmic reticulum Ca-ATPase is not mediated by CaM, but is directed toward the enzyme molecule.

Animals↗
PubMed1984

[Effect of phenothiazines on Ca-ATPase in the sarcoplasmic reticulum of rabbit skeletal muscles].

The phenothiazines trifluoroperazine , chlorpromazine and etmozine inhibit Ca-ATPase of the sarcoplasmic reticulum of rabbit skeletal muscles. The inhibitory action decreases in the order of trifluoroperazine greater than chlorpromazine greater than etmozine . The data are provided, indicating that the inhibitory effects of the phenothiazines on Ca-ATPase of the reticulum of the skeletal muscles are not mediated via calmodulin.

Animals↗
PubMed1984

[Study of electromechanical coupling in smooth muscle cells of the ureter using phenothiazines].

Chlorpromazine (ClP) and trifluoperazine (TFP) depress electrical and mechanical activity of ureter smooth muscle cells. Contraction was depressed by less doses of the substances applied as compared with the processes responsible for generation of spike activity. ClP causes the displacement of the dose-effect curve for Ca2+ towards larger concentrations of the latter. Trifluoperazine displaces the dose-effect curve for contraction to the right and downwards. It is concluded that inhibition of contraction and depression of ClP and TFP spikes is due to the calmodulin blocking on which kinase activity of myosin light chains depends. It is supposed that processes responsible for activation of the membrane systems of Ca2+ transport in the process of spike generation are also calmodulin-dependent.

Animals↗