Activation of μ-opiate receptors as a factor of regulation of heart resistance to ischemia-reperfusion and oxidative stress

Intravenous injection of the selective μ-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages.In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusionin vitro. Furthermore, stimulation of μ-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe²⁺ and ascorbic acid.     

Effect of synthetic analogs of dermorphin on mitosis in the corneal and lingual epithelium of albino rats

A study of the effects of synthetic analogs of dermorphin which are prime agonists of the μ-opiate receptors, on cell division in the corneal and lingual epithelium of albino rats showed that both analogs depressed DNA synthesis in the corneal and lingual epithelium 4 h after administration. In the lingual epithelium DNA synthesis and the mitogenic index were still depressed 24 h after drug administration. In the cornea cell division parameters had normalized by this time. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 508–510, November, 1994 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

The effect of μ-and σ-opiate receptor agonists on cell division of corneal and tongue epithelium in albino rats

The effect of μ- and σ-opiate receptor agonists at 10 μg/kg on the processes of cell division in corneal and tongue epithelium of albino rats is studied using the method of autoradiography with³H-thymidine. The ligand of the μ-receptors causes the inhibition of DNA synthesis in corneal epithelium 4, 12, and 24 h later and lowers the mitotic index after 4 and 24 h. In contrast, in the tongue epithelium stimulation of the proliferative processes occurs. Ligand of the σ-receptors stimulates DNA synthesis in corneal epithelium after 12 and 24 h and cell division after 12 h. In the tongue epithelium DNA synthesis is activated after 4, 12, and 24 h and cell division after 12 h. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 533–535, May, 1994 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Contribution of μ- and δ-opiate receptors into vagotropic effect of met-enkephalin

In anesthetized cats met-enkephalin affects the initial cardiac rhythm and synchronizing component of vagal chronotropic control via excitation of δ-opiate receptors and modulates tonic inhibitory vagal control via activation of both δ- and μ-opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 502–505, November, 1998     

Participation of opioid and serotoninergic brain receptors in amphetamine-induced stereotypy and hyperthermy

The inbred rat strains WAG and Fischer-344 were found to differ in the duration of amphetamine-induced stereotypy and the degree of hyperthermy elicited by this drug, the stereotypy lasting longer in WAG rats and the hyperthermy being more pronounced in Fischer—344 rats. A comparison of interstrain differences in the amphetamine effects, in receptor binding, and in the pharmacological activity of receptor agonists suggests that the μ-opiate system of the brain may be involved in the manifestation of amphetamine-induced stereotypy, while its serotoninergic system may mediate the elevation of body temperature caused by this drug. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, 242–243, September, 1995 Presented by V. N. Yarygin, Member of the Russian Academy of Medical Sciences     

Correction of electrical instability of the heart with opiate receptor ligands

Peripheral injections of the μ-opiate receptor agonist DALDA,k-opiate receptor agonist spiradoline, and δ-opiate receptor blocker DuP734 significantly increased the ventricular fibrillation threshold in animals with modeled postinfarction cardiosclerosis or stress-induced damage to the heart. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 399–401, October, 1998     

On the involvement of endogenous μ- and δ-opiate receptor agonists in the antiarrhythmic effect of adaptation

Rats adapted to stress showed a decreased severity and incidence of cardiac arrhythmias induced by epinephrine, and these effects of adaptation were abolished by naloxone. It is suggested that stress adaptation mitigates arrhythmia by activating the endogenous opioid system and stimulating the μ-opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 24–25, January, 1996 Presented by R. S. Karpov, Member of the Russian Academy of Medical Sciences     

The contribution of dopamine autoreceptors to the reactivating effect of opioid antagonists

The dopamine-opioid interaction is analyzed in amnesia and forgetfulness with the use of passive avoidance conditioning in experiments on mice. Naloxone or ICI174.864 administration restored the conditioned response in both learning situations against the background of saline. Pretreatment with (+)3PPP eliminated the reactivating effects of μ- and δ-opiate receptor blockade in the case of amnesia. The activation of dopamine autoreceptors in forgetfulness disrupted the memory restoration induced by ICI174.864, but not that by naloxone. The findings attest that reactivation of an amnestied memory trace by opioid receptor blockade depends on dopaminergic system functioning, whereas in the case of forgetfulness dopamine-opioid interactions are probably determined by the functional heterogeneity of the μ- and δ-opiate receptors and diminished contribution of the dopamine system to the process. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, No. 2, pp. 120–124, February, 1995 Presented by V. A. Trufakin, Member of the Russian Academy of Medical Sciences     

Prevention of experimental epinephrine-induced arrhythmias with agonists of δ1- and δ2-opiate receptors

Agonists of δ₁- and δ₂-opiate receptors prevent epinephrine-induced arrhythmias in rats after intracerebroventricular administration. The antagonist of δ-opiate receptors ICI 174,864 blocks antiarrhythmic effect of the selective agonist of δ-opiate receptors DTLET and exhibits no antiarrhythmic activity by itself. It is shown that antiarrhythmic effect of DTLET is associated with increased vagal tone. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 286–288, September, 1997     

Peripheral μ-Opiate receptors and modulation of myocardial tolerance to arrhythmogenic stimuli

The peripheral μ-opiate receptor agonists DALDA and PL017 are highly effective against arrhythmias induced by adrenaline, aconitine, or CaCl₂. The effect was abolished by the μ-opiate receptor antagonist CTAP. It is likely that Ca-channel block is involved in antiarrhythmic effect of DALDA. Translated fromByulleten' Eksperimental'noi Biologii 1 Meditsiny, Vol. 125, No. 6, pp. 650–653, June, 1998     

Cardioprotective effects of stimulation of peripheral μ-opiate receptors and the role of opiatergic mechanisms in the pathogenesis of stress-induced heart damage

Immobilization induces stress damage to the heart. DAGO, an agonist of μ-opiate receptors potentiates, while an agonist of peripheral μ-opiate receptors prevents this damage. Naltrexone reduces, while methylnaltrexone, an inhibitor of peripheral μ-opiate receptors, potentiates the stress-induced damage to the heart. Other opiate ligands have no effect on heart damage. It is suggested that the stress-induced damage to the heart is promoted by activation of central μ-opiate receptors and prevented by stimulation of peripheral μ-opiate receptors. Translated fromByulleten'Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 276–278, March, 1997     

Modulating effect of μ-opiate receptor ligands on adrenergic stage in pathogenesis of stress-induced damage to the heart

The agonists of μ-opiate receptors, DAGO and DALDA, prevent stress-induced enhancement of^99mTc-pyrophosphate accumulation in the myocardium, which attests to cardioprotective activity of these opioids. This phenomenon is presumably related to modulating effect of these agents on the adrenergic stage in pathogenesis of stress-induced damage to the heart. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 510–512, November, 1998     

Antiarrhythmic effects of μ-opiate receptor agonists in rats with epinephrine-induced arrhythmias: Role of the vegetative nervous system

The μ-opiate receptor agonists DAGO and DALDA preinjected intravenously in a dose of 0.1 mg/kg prevented the occurrence of arrhythmias in rats injected with epinephrine. Their antiarrhythmic activity was not modified by atropine or hexamethonium. It is concluded that the vegetative nervous system plays no substantial role in mediating the antiarrhythmic effects of DAGO and DALDA, and that these effects are most likely associated with stimulation of cardiac opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 25–27, July, 1996     

Activation of μ-opiate receptors as a factor of regulation of heart resistance to ischemia-reperfusion and oxidative stress

Intravenous injection of the selective μ-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages.In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusionin vitro. Furthermore, stimulation of μ-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe²⁺ and ascorbic acid. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 163–167, August, 2000     

Vestibuloprotective activity of seal serum proteins

Cat and rat experiments show that the protein fraction isolated from blood serum of the Greenland seal has a protective activity against motion sickness. This activity is comparable to that of the classical vestibuloprotector scopolamine and is greater than that of diprazine. Radioligand assay of the receptor binding showed that the serum protein fraction has the highest affinity for α₂-adrenoceptors, μ-opioid, and benzodiazepine receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol 117, N ^o 4, pp. 444–445, April, 1994     

Impact of preliminary gamma-irradiation on the pattern of change in vascular tone after intravenous injection ofNeisseria meningitidis lipopolysaccharide in rats

It is shown on rats that intravenous administration of theNeisseria menignitidis lipopolysaccharide lowers the mean arterial pressure, myocardial contractility and vascular tone in the system of the left carotid artery. In rats exposed to gamma radiation and then to the lipopolysaccharide, the decrease in myocardial contractility and the degree of arterial hypotension were more pronounced than in those exposed to the lipopolysaccharide alone, but the vascular tone in the carotid artery system was reduced to a lesser extent. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 129–131, August, 1995 Presented by V. A. Matyukhin, Member of the Russian Academy of Medical Sciences     

Relationship between blood supply to myocardial segments and their contractility in dogs with intact and ischemic myocardium

In dogs with an intact heart, intravenously administered dipyridamole increased the contractility of a myocardial segment 30–80% and the volume rate of coronary blood flow 142±14%. Dipyridamole administered to dogs before their coronary artery was occluded for 3 min did not decrease the contractility of the ischemia-affected myocardial segment. In dipyridamole-treated dogs with well-developed collaterals, blood was redistributed to the intact zone and the blood flow in the vein draining the ischemic zone increased by 168±17%. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 11, pp. 473–477, November, 1995 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Adaptation to hypoxia,unlike adaptation to stress,fails to protect the isolated heart from reperfusion after total ischemia (An NMR study)

Effects of adaptation to hypoxia on the contractility of isolated rat hearts and on their levels of ATP and inorganic phosphate after total ischemia were evaluated. This adaptation failed to render the cardiac energy-supplying system more resistant to postischemic reperfusion and thus did not accelerate the restoration of cardiac contractility after ischemia. The results of adaptation to hypoxia were then compared with those of adaptation to stress, which had been shown to bring about a marked increase in cardiac resistance to postischemic reperfusion. It is concluded that the profound differences noted between the cardioprotective effects of these two forms of adaptation are due to a much greater accumulation of stabilizing proteins from the HSP70 family during adaptation to stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 11, pp. 481–484, November, 1995 Presented by N. R. Paleev, Member of the Russian Academy of Medical Sciences     

Impact of 13(S)-HPODE,a lipoxygenase product of linoleic acid,on calcium transport and Na,K-ATPase activity in the myocardial sarcolemma

In thisin vitro study using a purified sarcolemmic fraction of guinea pig myocardium, the 13(S)-hydroperoxide of linoleic acid (13-HPODE) increased in a dose-dependent manner the permeability of myocardial sarcolemma to Ca ions in concentrations above 10 μmol/liter, stimulated Na/Ca exchange there in concentrations from 0.1 to 10 μmol/liter, and exerted a digitalis-like action on sarcolemmic Na,K-ATPase in concentrations between 0.1 and 100 μmol/liter (IC₅₀=20 μmol/liter). The results indicate that the linoleic acid hydroperoxide may be an effective modulator of sarcolemmic Ca²⁺ transport and of membrane-bound enzymes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 255–257, September, 1995 Presented by D. F. Chebotarev, Member of the Russian Academy of Medical Sciences     

Effect of μ-opiate receptor agonist tetrapeptide A10 on DNA synthesis and protein content in the myocardium of albino rats

Effect of intraperitoneal injection of tetrapeptide A10 (H-Tyr-D-Orn-Phe-Gly-OH), selective μ-opiate receptor agonist, synthetic analog of dermorphine, in a dose of 100 μg/kg on DNA synthesis and protein content in the myocardium was studied in albino rats. Five injections of tetrapeptide on days 2–6 after birth caused no changes in DNA synthesis 17 days after the last injection,i. e. in 24-day rats. The number of nucleoli and their area increased. In adult males long-term (3-week) treatment with tetrapeptide A10 increased the number of nucleoli and the mean and integral optical density of isolated cardiomyocytes stained with amido black B, which probably attested to activation of protein synthesis in the myocardium. Simultaneously, the content of catecholamines in the heart increased. These data are comparable with delayed effects of κ-opiate receptor agonist dinorphine A_1–13 and indicate that morphogenetic properties of opioid peptides in rat myocardium are realized via the same routes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 12, pp. 693–695, December, 2000