Browsing by Author "Baumane, Larisa"

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    Functional evaluation of THIQ, a melanocortin 4 receptor agonist, in models of food intake and inflammation
    (2007-12) Muceniece, Ruta; Zvejniece, Liga; Vilskersts, Reinis; Liepinsh, Edgars; Baumane, Larisa; Kalvinsh, Ivars; Wikberg, Jarl E.; Dambrova, Maija
    The central melanocortinergic system plays an important role in regulating different aspects of energy homeostasis and the immunomodulatory response. In the present study, we evaluated the in vivo activities of food intake suppression and anti-inflammatory activity of THIQ, which has been proposed to possess high and selective melanocortin-4 receptor agonistic activity in vitro. The results showed that THIQ (0.1, 0.3 and 1 nmol/rat, intracerebroventricularly) is less effective in reducing food intake and body weights of rats than the non-selective melanocortin receptor agonist melanotan II. Electron paramagnetic resonance measurements in mice brain tissue showed that THIQ at doses of 0.001 and 0.01 nmol/mouse (intracisternally) increased the concentration of nitric oxide, which is not typical for melanocortin receptor agonists. In an experimental brain inflammation model, THIQ only weakly antagonized lipopolysaccharide-induced nitric oxide overproduction in brain tissue at a dose of 0.01 nmol/mouse. Our findings provide new insight into the in vivo pharmacological profile of the in vitro selective melanocortin-4 receptor agonist THIQ and give grounds for caution when interpreting and predicting melanocortin receptor selective agonist activity in vivo.
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    Investigations on the pharmacology of the cardioprotective guanidine ME10092
    (2004-08) Dambrova, Maija; Liepinsh, Edgars; Kirjanova, Olga; Petrovska, Ramona; Pugovich, Osvalds; Baumane, Larisa; Uhlen, Staffan; Kalvinsh, Ivars; Oliver, Douglas; Wikberg, Jarl E.S.
    The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)- guanidine), which possesses a strong cardioprotective effect to ischemia-reperfusion, was assessed for different pharmacological actions that may underlie its cardioprotective effect. In the living rat ME10092 decreased the blood pressure and heart rate in a dose-dependent manner. We found ME10092 to bind to α1- and α2-adrenoreceptors with moderate affinity (Ki values 1-4 μM), and to block adrenaline-elicited contractile responses in isolated guinea pig aortas. Our results indicate that ME10092 possesses a certain anti-oxidant profile. Thus, in a competitive manner and with low affinity it inhibited the bovine milk xanthine oxidase enzyme, as well as NAD(P)H oxidase driven oxyradical formation in membrane fractions isolated from the rat brain. By using electron paramagnetic resonance we here show that, after its systemic administration, ME10092 modulates the nitric oxide (NO) content in several tissues of the rat in a time-dependent manner. However, in vitro ME10092 inhibited the activities of nitric oxide synthases nNOS and eNOS, but not that of iNOS. Our data give evidence that the cardioprotective effect of ME10092 could be mediated through pharmacological mechanisms that include some modulation of NO production, as well as possible inhibition of radical formation during ischemia-reperfusion.