Composto sulfonilidrazônico, processo de obtenção do composto sulfonilidrazônico e composições farmacêuticas

DepositadaDescreve um composto de certa fórmula, seu processo de obtenção e uso na fabricação de uma composição farmacêutica para estimular a produção de insulina. Especificamente, a presente invenção compreende uma série de sulfonilidrazonas que podem ser utilizadas na fabricação de uma composição farmacêutica para tratar diabetes. A presente invenção se situa nos campos da farmácia e da química

The stimulatory effect of angiotensin II on Na+-ATPase activity involves sequential activation of phospholipases and sustained PKC activity

AbstractAngiotensin II (Ang II) stimulates the proximal tubule Na+-ATPase through the AT1 receptor/phosphoinositide phospholipase Cβ (PI-PLCβ)/protein kinase C (PKC) pathway. However, this pathway alone does not explain the sustained effect of Ang II on Na+-ATPase activity for 30 min. The aim of the present work was to elucidate the molecular mechanisms involved in the sustained effect of Ang II on Na+-ATPase activity. Ang II induced fast and correlated activation of Na+-ATPase and PKC activities with the maximal effect (115%) observed at 1 min and sustained for 30 min, indicating a pivotal role of PKC in the modulation of Na+-ATPase by Ang II. We observed that the sustained activation of PKC by Ang II depended on the sequential activation of phospholipase D and Ca2+-insensitive phospholipase A2, forming phosphatidic acid and lysophosphatidic acid, respectively. The results indicate that PKC could be the final target and an integrator molecule of different signaling pathways triggered by Ang II, which could explain the sustained activation of Na+-ATPase by Ang II

Entamoeba histolytica : ouabain-insensitive Na+-ATPase activity

6 p. : il.Our aim was to determine the presence of sodium pumps in Entamoeba histolytica. It is shown through the measurement of ouabainsensitive ATPase activity and immunoblotting that E. histolytica does not express (Na++K+)ATPase. On the other hand, we observed a Na+-ATPase with the following characteristics: (1) stimulated by Na+ or K+, but these effects are not addictive; (2) the apparent affinity is similar for Na+ and K+ (K0.5 = 13.3 ± 3.7 and 15.4 ± 3.1 mM, respectively), as well as the Vmax (24.9 ± 1.5 or 27.5 ± 1.6 nmol Pi mg 1 min 1, respectively); (3) insensitive up to 2 mM ouabain; and (4) inhibited by furosemide with an IC50 of 0.12 ± 0.004 mM. Furthermore, this enzyme forms a Na+- or K+-stimulated, furosemide- and hydroxylamine-sensitive ATP-driven acylphosphate phosphorylated intermediate

Involvement of the G(i/o)/cGMP/PKG pathway in the AT(2)-mediated inhibition of outer cortex proximal tubule Na(+)-ATPase by Ang-(1–7)

The molecular mechanisms involved in the Ang-(1–7) [angiotensin-(1–7)] effect on sodium renal excretion remain to be determined. In a previous study, we showed that Ang-(1–7) has a biphasic effect on the proximal tubule Na(+)-ATPase activity, with the stimulatory effect mediated by the AT(1) receptor. In the present study, we investigated the molecular mechanisms involved in the inhibition of the Na(+)-ATPase by Ang-(1–7). All experiments were carried out in the presence of 0.1 nM losartan to block the AT(1) receptor-mediated stimulation. In this condition, Ang-(1–7) at 0.1 nM inhibited the Na(+)-ATPase activity of the proximal tubule by 54%. This effect was reversed by 10 nM PD123319, a specific antagonist of the AT(2) receptor, and by 1 μM GDP[β-S] (guanosine 5′-[β-thio]diphosphate), an inhibitor of G protein. Ang-(1–7) at 0.1 M induced [(35)S]GTP[S] (guanosine 5′-[γ-[(35)S]thio]triphosphate) binding and 1 μg/ml pertussis toxin, an inhibitor of G(i/o) protein, reversed the Ang-(1–7) effect. Furthermore, it was observed that the inhibitory effect of Ang-(1–7) on the Na(+)-ATPase activity was completely reversed by 0.1 μM LY83583, an inhibitor of guanylate cyclase, and by 2 μM KT5823, a PKG (protein kinase G) inhibitor, and was mimicked by 10 nM d-cGMP (dibutyryl cGMP). Ang-(1–7) increased the PKG activity by 152% and this effect was abolished by 10 nM PD123319 and 0.1 μM LY83583. Taken together, these data indicate that Ang-(1–7) inhibits the proximal tubule Na(+)-ATPase by interaction with the AT(2) receptor that subsequently activates the G(i/o) protein/cGMP/PKG pathway

The effect of saponins from <it>Ampelozizyphus amazonicus</it> Ducke on the renal Na⁺ pumps’ activities and urinary excretion of natriuretic peptides

<p>Abstract</p> <p>Background</p> <p>In a previous study, we showed that a saponin mixture isolated from the roots of <it>Ampelozizyphus amazonicus</it> Ducke (SAP<it>Aa</it>D) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAP<it>Aa</it>D- induced antidiuresis in rats.</p> <p>Methods</p> <p>To evaluate the effect of SAP<it>Aa</it>D on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAP<it>Aa</it>D (<it>SAPAaD + Furo</it>) or 0.5 ml of 0.9 % NaCl (<it>NaCl + Furo</it>). In the <it>SAPAaD + NaCl</it> group, rats were pretreated with SAP<it>Aa</it>D and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na⁺ pumps on antidiuretic effects promoted by SAP<it>Aa</it>D, rats were given the physiological solution (as above) containing SAP<it>Aa</it>D (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na⁺- and (Na⁺,K⁺)-ATPases were calculated from the difference between the [³²P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively.</p> <p>Results</p> <p>It was observed that SAP<it>Aa</it>D inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, <it>NaCl + Furo</it> group, n = 5, to 5.9 ± 1.0 mL, <it>SAPAaD + Furo</it> group n = 5, p < 0.05), increased both Na⁺-ATPase (from 25.0 ± 5.9 nmol Pi.mg^-1.min^-1, control, to 52.7 ± 8.9 nmol Pi.mg^-1.min^-1, p < 0.05) and (Na⁺,K⁺)-ATPase (from 47.8 ± 13.3 nmol Pi.mg^-1.min^-1, control, to 79.8 ± 6.9 nmol Pi .mg^-1.min^-1, p < 0.05) activities in the renal cortex. SAP<it>Aa</it>D also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP.</p> <p>Conclusion</p> <p>We concluded that the SAP<it>Aa</it>D antidiuretic effect may be due to an increase in the renal activities of Na⁺- and (Na⁺,K⁺)-ATPases and/or a decrease in the renal ANP.</p