Neurite outgrowth induced by stimulation of angiotensin II AT receptors in SH-SY5Y neuroblastoma cells involves c-Src activation.

Neuroblastoma, the most common extracranial solid tumor occurring in childhood, originates from the aberrant proliferation of neural crest cells. Accordingly, the mechanism underling neuronal differentiation could provide new strategies for neuroblastoma treatment. It is well known that neurite outgrowth could be induced by Angiotensin II (Ang II) AT receptors; however, the signaling mechanism and its possible interaction with NGF (neural growth factor) receptors remain unclear.

Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates apoptosis mediated by angiotensin II AT receptors.

Apoptosis plays an important role in cellular processes such as development, differentiation, and homeostasis. Although the participation of angiotensin II (Ang II) AT receptors (AT R) in cellular apoptosis is well accepted, the signaling pathway involved in this process is not well established. We evaluated the participation of signaling proteins focal adhesion kinase (FAK), RhoA, and p38 mitogen-activated protein kinase (p38MAPK) in apoptosis induced by Ang II via AT R overexpressed in HeLa cells.

Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats.

The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension and pulmonary fibrosis. In the present study, we examined the effects of maternal exposure to captopril (2.85 mg/kg/day) during late pregnancy (G13-G21) on postnatal rat lung development.

AT₂receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain.

The functional role of AT(2) receptors is unclear and it activates unconventional signaling pathways, which in general do not involve a classical activation of a G-protein. In the present study, we aimed to investigate the transduction mechanism of AT(2) Ang II receptors in PND15 rat hindbrain membrane preparations, which represents a physiological developmental condition. To determine whether Ang II AT(2) receptors induced association to SHP-1 in rat hindbrain, co-immunoprecipitation assays were performed.

Purkinje cells express Angiotensin II AT(2) receptors at different developmental stages.

Angiotensin II (Ang II) binds and activates two major receptors subtypes, namely AT(1) and AT(2). In the fetus, AT(2) receptors predominate in all tissues and decline shortly after birth, being restricted to a few organs including brain. Interpretation of the function of Ang II in the cerebellum requires a thorough understanding of the localization of Ang II receptors.

Role of IRS-4 in PI3-K activation by insulin in HepG2 cells, modulation by Angiotensin II.

Insulin receptor substrate-4 (IRS-4) has a limited tissue expression and its modulation by tyr-phosphorylation is still controversial. We evaluated the participation of IRS-4 in the cross-talk between Angiotensin II (Ang II) and Insulin (Ins) receptors in HepG2 cells. Ins (10(-7)M) induced tyr-phosphorylation of IRS-4 (maximal at 5 min), an effect potentiated by Ang II AT(1) receptors.

Prenatal blockade of Ang II receptors affects neonatal rat hindbrain structure and receptor localization.

The development of knock-out mice for Angiotensin II (Ang II) AT(2) receptors, which exhibited altered exploratory behavior, prompted us to investigate the cerebellum and brainstem. We evaluated the effect of stimulation/inhibition of Ang II receptors on hindbrain development, in offspring (postnatal days P0, P8) of pregnant rats treated during late pregnancy (Ang II, Losartan or PD123319, 1 mg/kg/day). Receptor localization by autoradiography showed in P0 and P8 hindbrains, that most structures expressed AT(2) subtype: cerebellar cortex, cerebellar nuclei, genu facial nucleus, inferior colicullus, inferior olive.

Involvement of c-Src tyrosine kinase in SHP-1 phosphatase activation by Ang II AT2 receptors in rat fetal tissues.

Angiotensin II (Ang II) AT(2) receptors are abundantly expressed in rat fetal tissues where they probably contribute to development. In the present study we examine the effects of Ang II type 2 receptor stimulation on SHP-1 activation. Ang II (10(-7) M) elicits a rapid and transient tyrosine phosphorylation of SHP-1, maximal at 1 min, in a dose-dependent form, blocked by the AT(2) antagonist, PD123319.

Inhibition of Angiotensin II receptors during pregnancy induces malformations in developing rat kidney.

Evidence suggests that Angiotensin II plays an important role in the complex process of renal organogenesis. Rat kidney organogenesis starts between E13-14 and lasts up to 2 weeks after birth. The present study demonstrates histologic modifications and changes in receptor localisation in animals born from mothers treated with Angiotensin II, Losartan or PD123319 (1.

Angiotensin II type 1 receptor A1166C gene polymorphism and essential hypertension in San Luis.

Essential hypertension is considered a multifactorial trait resulting from a combination of environmental and genetic factors. The angiotensin II type 1 receptor mediates the vasoconstrictor and growth-promoting effects of Ang II. The A1166C polymorphism of the AT1 receptor gene may be associated with cardiovascular phenotypes, such as high arterial blood pressure, aortic stiffness, and increased cardiovascular risk.

Angiotensin II modulates tyr-phosphorylation of IRS-4, an insulin receptor substrate, in rat liver membranes.

Angiotensin II (Ang II), a major regulator of blood pressure, is also involved in the control of cellular proliferation and hypertrophy and might exhibit additional actions in vivo by modulating the signaling of other hormones. As hypertension and Insulin (Ins) resistance often coexist and are risk factors for cardiovascular diseases, Ang II and Insulin signaling cross-talk may have an important role in hypertension development. The effect of Ins on protein tyrosine phosphorylation was assayed in rat liver membrane preparations, a rich source of Ins receptors.

Angiotensin II mediates Tyr-dephosphorylation in rat fetal kidney membranes.

Angiotensin II (Ang II) elicits a variety of physiological effects through specific Ang II receptors in numerous tissues. In addition, Ang II is a modulator of cellular growth and exerts a positive or negative effect on cell growth depending on which receptor subtype is activated. Expression of the intrarenal AT2 receptors occurs at its highest levels in the fetal kidney, with a rapid decline after birth.

Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach.

Nitric oxide (NO) has become an important intracellular and intercellular signal molecule and inhibition of the enzyme which produces NO (NOS, NO synthase) become a major goal for pharmacological researchers. We performed a complete search for the lowest-energy conformations at the AM1 calculation level, for zwitter-ionic species of NOS inhibitors, analogs to L-Arg. The lowest- energy conformations obtained were fully optimized at the ab initio theory levels: HF/3-21G and HF/6-31G*.