Selective pharmacological blockade of synaptic transmission in parasympathetic pathways to the heart in rats

The blocking effects of newly synthesized compounds N-decyltropine bromide (IEM-1556) and its derivatives N-methyltropine iodide (IEM-1893) and N-hexyltropine iodide (IEM-1848), possessing aliphatic radicals of different length, on the vagus-induced reduction of the heart rate were studied in acute experiments on rats. The effects produced by these compounds on the level of arterial blood pressure and synaptic transmission in the superior cervical ganglion (SCG) of the rat were studied and compared with those produced by classical ganglion-blocking agents (hexamethonium and trimetaphan) and muscle relaxants (pancuronium and decamethonium). IEM-1556 much more effectively blocked the vagus-induced reduction of the heart rate than other tested blocking agents, and, in contrast to the classical ganglion-blocking agents and decamethonium, did not reduce the arterial blood pressure. In addition, IEM-1556 was less effective than hexamethonium in blocking synaptic transmission through the SCG. IEM-1893 and IEM-1848 demonstrated lower efficacy in blocking SCG transmission, if compared with that of IEM-1556. The results suggest that IEM-1556 is a highly selective blocking agent for parasympathetic versus sympathetic pathways, and its selectivity is determined by the presence of a decyl aliphatic radical in its molecule.Neirofiziologiya/Neurophysiology, Vol. 27, No. 5/6, pp. 323–330, September–December, 1995.     

Role of κ1 opioid receptors and cAMP in regulation of cardiac tolerance to ischemia and reperfusion

The cardioprotective, inotropic, and antiarrhythmic effects of U-50.488, a selective agonist of κ₁ opioid receptors (κ₁ ORs), was studied using the model of 45-min total ischemia and 30-min reperfusion of isolated rat heart. Cardiac κ₁ ORs were stimulated by adding U-50.488 to the perfusing solution up to the final concentration of 0.1 or 1 μmol/l. The opioid had no influence on the incidence of reperfusion arrhythmias. The addition of 0.1 μmol/l U-50.488 reduced the reperfusion release of creatine phosphokinase (CPK) by half, which positively correlated with the decrease in the myocardial cAMP content (r = 0.89, p < 0.01). At the same time, the addition of U-50.488 in the higher concentration (1 μmol/l) had no effect on either cAMP level or CPK release. These results indicate that the cardioprotective effect of U-50.488 may be connected with the reduction of myocardial cAMP content. Activation of κ₁ ORs caused a decrease in both frequency and amplitude of myocardial contractions. The negative inotropic and chronotropic effect of U-50.488 was shown to be independent of changes in the myocardial cAMP content. A hypothesis is proposed that the absence of any cardioprotective effect of U-50.488 at the higher concentration (1 μmol/l) is accounted for by its interaction with unknown nonopioid receptors of cardiac myocytes.     

Role of a Tetraethylammonium-Sensitive Component of Potassium Currents in High-Frequency Tonic Impulsation Generated by Rat Retinal Ganglion Cells

Using the voltage/current clamp technique in the whole-cell configuration, we studied the role of the highly tetraethylammonium (TEA) -sensitive component of integral potassium current in the generation of high-frequency tonic impulsation by rat retinal ganglion cells (RGCs). Application of 0.5 mM TEA led to a decrease in the frequency of evoked tonic impulsation by RGCs by 63% (from 55 ± 10 sec^–1 in the control to 26 ± 5 sec^–1 in the presence of the blocker; n = 11). In this case, the duration of single action potentials at the level of 50% their amplitude increased by 64% (from 1.1 ± 0.1 to 1.8 ± 0.1 msec; n = 11), the rate of repolarization decreased by 54% (from −101 ± 9 to −46 ± 5 mV/msec; n = 11), and the amplitude of afterhyperpolarization dropped by 62% (from −16 ± 2 to −6 ± 2 mV; n = 11). Upon the action of 0.5 mM TEA, the amplitude of the integral potassium current in RGCs decreased; the current component sensitive to the above blocker was equal to 0.41 ± 0.05 nA (n = 6), while the respective value in the control was 1.62 ± 0.14 nA (n = 12). Thus, a moderate (on average, by 25%) decrease in the amplitude of the above potassium current significantly influenced the characteristics of impulse activity generated by RGCs. The TEA-sensitive component of the current was similar to the Kv3.1/Kv3.2 potassium current described earlier. The obtained data are indicative of the key role of the highly TEA-sensitive component of the potassium current (passed probably via Kv3.1/Kv3 channels) in high-frequency tonic activity generated by RGCs.     

Uncoupling proteins and their role in the regulation of brain and heart tolerance to impact of ischemia and reperfusion

Experimental data indicate that moderate uncoupling oxidative phosphorylation induces reduction in production of reactive oxygen species (ROS) and promotes an increase in survival of neurons and cardiomyocytes under hypoxia and re-oxygenation conditions. Uncoupling proteins (UCP) are expressed by cardiomyocytes and neurons. These proteins are involved in the thermogenesis, inhibit ROS generation by mitochondria, reduce deltaphi, elevate respiration rate of these organelles. It was established that UCP contributed to the elevation of cardiomyocyte and neuron tolerance of an impact of hypoxia and re-oxygenation. They also promote cell resistance to oxidative stress. Experimental data indicate the important role of the UCP in the neuroprotective and cardioprotective effects of ischemic preconditioning. At the same time, real contribution of the UCP in preconditioning is still to be verified.     

Discovery and barcoding by analysis of spliced leader RNA gene sequences of new isolates of Trypanosomatidae from Heteroptera in Costa Rica and Ecuador

Trypanosomatid diversity in Heteroptera was sampled using a culture-independent approach based on amplification and sequencing of Spliced Leader RNA gene repeats from environmental samples. By combining the data collected herein with that of previous work, the prevalence of parasites was found to be 22%-23%. Out of approximately 170 host species investigated nearly 60 were found to harbor trypanosomatids. The parasites found were grouped by cluster analysis into 48 typing units. Most of these were well separated from the known groups and, therefore, likely represent new trypanosomatid species. The sequences for each typing unit serve as barcodes to facilitate their recognition in the future. As the sampled host species represent a minor fraction of potential hosts, the entire trypanosomatid diversity is far greater than described thus far. Investigations of trypanosomatid diversity, host-specificity, and biogeography have become feasible using the approach described herein.     

Parameters of proteome evolution from histograms of amino-acid sequence identities of paralogous proteins

Background  

The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic parameters of these three basic processes is contained in the proteome-wide distribution of sequence identities of pairs of paralogous proteins.