[The interaction of mu-opioid receptors with intracellular signal systems].

Review is devoted a modem state of researches of micro-opioid receptor. It is discussed literature data on the integration of micro-opioid receptor with adenylyl cyclase, phospholipase A2, C and D. It is analyzed reports on the interaction of micro-opioid receptor with NO-synthase and guanylyl cyclase.

Selective cannabinoid receptor agonist HU-210 decreases pump function of isolated perfused heart: role of cAMP and cGMP.

The rate and strength of heart contractions decreased after 10-min perfusion of rat myocardium with Krebs-Henseleit solution containing a selective cannabinoid receptor agonist HU-210 in a final concentration of 10 nM. HU-210 completely blocked the positive inotropic and chronotropic effect of beta-adrenoceptor agonist isoproterenol, decreased the basal level of cAMP, and abolished the isoproterenol-induced increase in myocardial cAMP concentration. cGMP concentration remained unchanged under these conditions.

Role of endogenous opioid receptor agonists in regulation of heart resistance to the arrhythmogenic action of short-term ischemia and reperfusion.

Preliminary selective block of mu-, delta1-, delta2-, and kappa-opioid receptors had no effect on the incidence of ventricular arrhythmias during 10-min coronary occlusion-reperfusion in ketamine-narcotized rats. Repetitive short-term immobilization of rats for 2 weeks improved heart resistance to the arrhythmogenic action of coronary occlusion and reperfusion. Selective mu-opioid receptor antagonist CTAP completely abolished, while selective delta- and kappa-opioid receptor antagonists did not modulate the antiarrhythmic effect of adaptation.

[Regulation by opiod peptides of the antioxidant enzyme activity and the prostanoid system in myocardium during stress].

The six hour stress in rats was modeled by the method of O. Desiderato. Cardiac damage was estimated by myocardial uptace of radioactive 99Tc-pyrophosphate.

[The antiarrhythmic effect of (-)-U-50,488 in rats with acute ischemia and reperfusion of heart is mediated by kappa1-opioid receptor activation].

Pretreatment with a selective kappa1 opioid receptor (OR) agonist (-)-U-50,488 (1 mg/kg, i.v.) prevented the development of arrhythmias induced by occlusion (10 min) and reperfusion (10 min) in ketamine anesthetized rats, while the treatment with a less active enantiomer (+)-U-50,488 in the same dose produced no such effects.

[The mechanism of antiarrhythmic action of the endogenous ORL1 receptor agonist nociceptin].

Prophylactic intravenous (i.v.) injections of a selective agonist of ORL1 receptors nociceptin (orphanin FQ) in a dose of 0.

[Delta-opioid receptor agonists prevent the irreversible damage of cardiomyocytes in ischemized-reperfused isolated rat heart].

Pretreatment with selective delta-opioid receptor (delta-OR) agonists decreased the level of creatine kinase in the coronary effluent of isolated rat heart during a 45-min global ischemia and a 30-min reperfusion. The effect was completely abolished after pretreatment of the delta-OR antagonist nitrindole. At the same time, pretreatment with mu-OR antagonists did not affect the level of creatine kinase in the coronary effluent.

Delta-opioid receptor antagonists exhibit properties of partial delta-receptor agonists in isolated perfused heart.

Perfusion of the isolated intact rat heart with Krebs-Henseleit solution containing agonists ((-)-TAN-67, DPDPE, and dalargin) or antagonists of delta-opioid receptors (naltrindole, TIPP[psi], and ICI 174,864) in a final concentration of 0.1 mg/liter was followed by a decrease in the heart rate, end-diastolic pressure, contraction rate, relaxation rate, and left ventricular developed pressure. Perfusion with a solution containing the delta-opioid receptor agonist DPDPE or delta-antagonists naltrindole, TIPP[psi], and ICI 174,864 before modeling of global ischemia increased the severity of reperfusion-induced contractile dysfunction in the myocardium.

Opioid receptors and heart resistance to arrhythmogenic factors.

We present detailed data on the role of central and peripheral opioid receptors in the regulation of heart resistance to arrhythmogenic factors. Stimulation of peripheral delta2- and kappa1-receptors increases heart resistance to the arrhythmogenic effect of acute ischemia and reperfusion. Activation of peripheral mu- and delta1-opioid receptors improves electrical stability of the heart in animals with postinfarction cardiosclerosis.

[Endogenic opioid peptides and antiarrhythmic effect of adaptation to stress].

Adaptation of rats to repeated short-term immobilization increases cardiac resistance to an arrhythmogenic action of coronary artery occlusion (10 min) and reperfusion (10 min) in rats anesthetized with ketamine and artificially ventilated. We examined the role of opioid receptors and endogenous opioid peptides in the development of this antiarrhythmic effect produced in response to repeated periods of immobilization stress. We found that repeated daily stress during a 15-day period resulted in an increase of leu-enkephalin in blood plasma, in the suprarenal gland and myocardium.

[The effect of dalargin and des-Tyr-dalargin on the functional state of intact and ischemized-reperfused myocardium].

Experiments on isolated perfused rat heart showed that dalargin, an antagonist of mu- and delta-opioid receptors, favors a decrease in the parameters of contractility of intact myocardium, while not influencing the pumping function (systolic and diastolic contractility) of reperfused myocardium. At the same time, des-Tyr-dalargin (the non-opioid analog of dalargin) suppresses the contractility of both the intact heart and the isolated myocardium subjected to global ischemia and reperfusion. Both dalargin and des-Tyr-dalargin reduced the incidence of reperfusion-induced arrhythmia, but did not affect the coronary flow before ischemia and after restoration of the coronary flow.

[Regeneration of myocardium].

It has been systematized modern data on the myocardial regeneration and the regulation of cardiac cell proliferation in mammals and man. It has been performed an analysis published works which indicate that cardiomyocyte division and DNA synthesis in myocardial cells increase in many times during different pathological conditions. It has been generalized and analyzed results of experimental and clinical researches on the participation of stem cells in the regeneration of the heart.

[Antiarrhythmic and cardioprotective effect of stimulation of delta1-opiate receptors in myocardial ischemia and reperfusion].

Pretreatment with intravenous peptide delta1-opioid receptor (OR) agonist DPDPE (0.5 mg/kg) decreases the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. The agonist of delta2-OR DSLET has no effect on arrhythmias in coronary artery occlusion and reperfusion.

[The effect of K(ATP)-channel activation on the electrical stability of myocardium in rats with postinfarction cardiosclerosis].

Opening of the ATP-dependent K-channels (K(ATP) channels) upon intravenous administration of the cardioselective activator BMS 180448 (3 mg/kg) decreased the ventricular fibrillation threshold (VFT) in rats with postinfarction cardiosclerosis (PIC). Preliminary injection of the selective K(ATP) channel blocker glibenclamide (0.3 mg/kg, i.

[Stimulation of the delta 1-receptors help to decrease reperfusion induced myocardial stunning].

In vivo or in vitro administration of a omega 1 receptor agonist d-SKF 10,047 (1 mg/kg intravenously or 10 mg/l in vitro) promoted an increase in the resistance of isolated perfused rat heart to ischemia/reperfusion injury. Both in vivo and in vitro stimulation of omega receptors prevents development of reperfusion contracture and release of creatine kinase and increases the developed pressure, double product, +dP/dt, and -dP/dt in the left ventricle. Activation of omega receptors has no significant effect on the occurrence of reperfusion arrhythmias ex vivo.

Effect of opiate peptide dalargin and des-Tyr-dalargin on cardiac pump function during ischemia-reperfusion.

Experiments on isolated perfused rat heart showed that nonselective micro- and delta-opiate receptor agonist dalargin decreased contractility of the intact heart, but had no effect on pump function of the ischemic myocardium. Dalargin analogue des-Tyr-dalargin not binding to opiate receptors decreased contractility of intact myocardium and isolated heart exposed to 45-min total ischemia. We hypothesize that the influence of dalargin is related to activation of cardiac delta-opiate receptors, while the inotropic effect of des-Tyr-dalargin is mediated by other receptors.

[The role of delta-1 opiate receptors in regulation of contractility in isolated rat heart during normal oxygenation and ischemia-reperfusion].

The experiments on isolated rat heart demonstrated significant decrease in reperfusion-induced damage of cardiomyocytes by addition of selective delta 1 receptor agonist DPDPE (0.1 mg/l) to the perfusion solution. On the contrary, no cardioprotective effect was observed for 0.

[The role of opiate receptors and ATP-dependent potassium channels of mitochondria in the formation of myocardial adaptive resistance to the arrhythmogenic effect of ischemia and reperfusion].

Preliminary stimulation of opiate receptors (ORs) by intravenous administration of mu agonist DALDA (0.5 mg/kg), delta 1 agonist DPDPE (0.5 mg/kg), and kappa agonist (-)-U-50.

[Alterations of inotropic function of isolated heart and extent of injury of cardiomyocytes after cannabinoid receptor activation during ischemia and reperfusion].

It was found that CB1- and CB2-receptor activation by intravenous administration of the selective CB-agonist HU-210 at a dose 0.1 mg/kg prompts an increase of myocardial resistance to the pathogenic action of ischemia and reperfusion in vitro. The revealed effects of HU-210 do not depend on the activation of CB-receptors in the myocardium.

[Peripheral effects of ligands of ORL1 receptors].

It has been discussed literature data on the role for ORL1 (NOR) receptors in the regulation of function of gastrointestinal, respiratory, cardiovascular, immune, endocrine systems. In addition, it has been discussed a possibility of penetration of blood brain barrier for ORL1 receptor ligands and species dependence of NOR-ligands' effects.

[Central effects of ORL1 receptor ligands].

It has been discussed literature data on molecular structure of ORL1 receptor and its interaction with intracellular signal systems and neurotransmitters. Data on chemical structure of ORL1 receptor ligands and their central effects (nociception, locomotion, feeding, cognition) are presented.

[Changes in cardiac resistance to arrhythmogenic effects during ATP-dependent K+ channel activation].

It has been found that pretreatment with ATP-dependent potassium channel (KATP-channel) opener, BMS 180448 (3 mg/kg, intravenously), increases cardiac resistance against arrhythmogenic action of coronary artery occlusion and reperfusion in anaesthetized rats. However, BMS 180448 induced a decrease in ventricular fibrillation threshold in rats postinfarction cardiac fibrosis. This effect was completely abolished by administration of the KATP-channel inhibitor, glibenclamide.