Plasminogen interaction with <i>Trypanosoma cruzi</i>

The ability of Trypanosoma cruzi to interact with plasminogen, the zimogenic form of the blood serin protease plasmin, was examined. Immunohistochemistry studies revealed that both forms, epimastigotes and metacyclic trypomastigotes, were able to fix plasminogen in a lysine dependant manner. This interaction was corroborated by plasminogen activation studies. Both forms of the parasite enhanced the plasminogen activation by tissue-type plasminogen activator.The maximal enhancements obtained were 15-fold and 3.4-fold with epimastigotes and metacyclic trypomastigotes, respectively, as compared to plasminogen activation in absence of cells. Ligand-blotting analysis of proteins extracted with Triton X-114 from a microsomal fraction of epimastigotes revealed at least five soluble proteins and one hydrophobic protein able to bind plasminogen

Effects of peripherally administered urotensin II and arginine vasotocin on the QT interval of the electrocardiogram in trout

International audienceThe QT interval of the electrocardiogram (ECG) is a measure of the duration of the ventricular depolarization and repolarization. In fish as in human, the QT interval is positively correlated with the RR interval of the ECG, a measure of the cardiac cycle length. Urotensin II (UII) is a neuropeptide that has been highly conserved from fish to human, and UII and its receptor (UT) are expressed in cardiovascular tissues including the heart. Although UII exerts potent cardiovascular actions, its possible effects on the QT interval have never been investigated. The goal of the present study was to provide insight into the potential effect of UII on the QT interval in an established in vivo trout model. To this end, the effects of UII on dorsal aortic blood pressure (PDA), RR, QT intervals and corrected QT (QTc) for RR interval, were investigated after intra-arterial (IA) injection of 5, 50 and 100 pmol UII. The effects of UII were compared to those of two structurally UII-related peptides (URPs), URP1 and URP2, and to those of arginine vasotocin (AVT), homolog of the mammalian arginine vasopressin. IA injection of vehicle or 5 pmol UII had no effect on the various parameters. At the 50-pmol dose, UII evoked its usual increase in PDA with a peak value observed 15 min after the injection (+22% from baseline, P<0.001). This hypertensive effect of UII was accompanied by a significant increase in the RR interval (+18%, P<0.001), i.e. a bradycardia, and these effects remained constant until the end of the recording. The highest dose of UII evoked similar hypertensive and bradycardic effects. Of interest, the QT interval did not change during the bradycardic action of UII (50 and 100 pmol) but the QTc interval significantly decreased. In trout pre-treated with urantide, a peptidic antagonist of UT, the hypertensive and bradycardic actions of 50 pmol UII were reduced 3-fold and no change occurred in the QT and QTc intervals. In trout pre-treated with blockers of the autonomic nervous system, the hypertensive effect of UII was maintained but no change appeared in RR, QT and QTc intervals. IA injections of 50 pmol URPs were without action on the preceding parameters. IA administration of 50 pmol AVT provoked quite similar increase in PDA, and elevation of the RR interval to those evoked by IA injection of UII but, in contrast to UII, AVT injection induced a highly significant and sustained prolongation of the QT interval compared to baseline (+7%, P<0.001) without change in QTc. Our results are indicative of a lack of QT interval change during UII-evoked bradycardia but not after AVT-induced bradycardia and suggest for the first time that some compensatory mechanism specific for the UII peptide is working to stabilize the QT interval. Further research is needed to elucidate the mechanism involved in this action of UII. The potential for UII to prevent detrimental prolongation of cardiac ventricular repolarization might be questioned

Central and Peripheral Effects of Urotensin II and Urotensin II-Related Peptides on Cardiac Baroreflex Sensitivity in Trout

International audienceThe baroreflex response is an essential component of the cardiovascular regulation that buffers abrupt changes in blood pressure to maintain homeostasis. Urotensin II (UII) and its receptor UT are present in the brain and in peripheral cardiovascular tissues of fish and mammals. Intracerebroventricular (ICV) injection of UII in these vertebrates provokes hypertension and tachycardia, suggesting that the cardio-inhibitory baroreflex response is impaired. Since nothing is known about the effect of UII on the cardiac baroreflex sensitivity (BRS), we decided to clarify the changes in spontaneous BRS using a cross spectral analysis technique of systolic blood pressure (SBP) and R-R interval variabilities after ICV and intra-arterial (IA) injections of trout UII in the unanesthetized trout. We contrasted the effects of UII with those observed for the UII-related peptides (URP), URP1 and URP2. Compared with vehicle-injected trout, ICV injection of UII (5-500 pmol) produced a gradual increase in SBP, a decrease in the R-R interval (reflecting a tachycardia) associated with a dose-dependent reduction of the BRS. The threshold dose for a significant effect on these parameters was 50 pmol (BRS; -55%; 1450 ± 165 ms/kPa vs. 3240 ± 300 ms/kPa; P < 0.05). Only the 500-pmol dose of URP2 caused a significant increase in SBP without changing significantly the R-R interval but reduced the BRS. IA injection of UII (5-500 pmol) caused a dose-dependent elevation of SBP. Contrasting with the ICV effects of UII, the R-R interval increased (reflecting a bradycardia) up to the 50-pmol dose while the BRS remained unchanged (50 pmol; 2530 ± 270 ms/kPa vs. 2600 ± 180 ms/kPa; P < 0.05). Nonetheless, the highest dose of UII reduced the BRS as did the highest dose of URP1. In conclusion, the contrasting effect of low picomolar doses of UII after central and peripheral injection on the BRS suggests that only the central urotensinergic system is involved in the attenuation of the BRS. The limited and quite divergent effects of URP1 and URP2 on the BRS, indicate that the action of UII is specific for this peptide. Further studies are required to elucidate the site(s) and mechanisms of action of UII on the baroreflex pathways. Whether such effects of central UII on the BRS exist in mammals including humans warrants further investigations

Divergent cardio-ventilatory and locomotor effects of centrally and peripherally administered urotensin II and urotensin II-related peptides in trout

International audienceThe urotensin II (UII) gene family consists of four paralogous genes called UII, UII-related peptide (URP), URP1 and URP2. UII and URP peptides exhibit the same cyclic hexapeptide core sequence (CFWKYC) while the N- and C-terminal regions are variable. UII, URP1, and URP2 mRNAs are differentially expressed within the central nervous system of teleost fishes, suggesting that they may exert distinct functions. Although the cardiovascular, ventilatory and locomotor effects of UII have been described in teleosts, much less is known regarding the physiological actions of URPs. The goal of the present study was to compare the central and peripheral actions of picomolar doses (5-500 pmol) of trout UII, URP1, and URP2 on cardio-ventilatory variables and locomotor activity in the unanesthetized trout. Compared to vehicle, intracerebroventricular injection of UII, URP1 and URP2 evoked a gradual increase in total ventilation (V TOT) reaching statistical significance for doses of 50 and 500 pmol of UII and URP1 but for only 500 pmol of URP2. In addition, UII, URP1 and URP2 provoked an elevation of dorsal aortic blood pressure (P DA) accompanied with tachycardia. All peptides caused an increase in locomotor activity (A CT), at a threshold dose of 5 pmol for UII and URP1, and 50 pmol for URP2. After intra-arterial (IA) injection, and in contrast to their central effects, only the highest dose of UII and URP1 significantly elevated V TOT and A CT. UII produced a dose-dependent hypertensive effect with concomitant bradycardia while URP1 increased P DA and heart rate after injection of only the highest dose of peptide. URP2 did not evoke any cardio-ventilatory or locomotor effect after IA injection. Collectively, these findings support the hypothesis that endogenous UII, URP1 and URP2 in the trout brain may act as neurotransmitters and/or neuromodulators acting synergistically or differentially to control the cardio-respiratory and locomotor systems. In the periphery, the only physiological actions of these peptides might be those related to the well-known cardiovascular regulatory actions of UII. It remains to determine whether the observed divergent physiological effects of UII and URPs are due to differential interaction with the UT receptor or binding to distinct UT subtypes