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Main Effector (main + effector)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Renin-angiotensin system revisited

JOURNAL OF INTERNAL MEDICINE, Issue 3 2008
F. Fyhrquist
Abstract. New components and functions of the renin-angiotensin system (RAS) are still being unravelled. The classical RAS as it looked in the middle 1970s consisted of circulating renin, acting on angiotensinogen to produce angiotensin I, which in turn was converted into angiotensin II (Ang II) by angiotensin-converting enzyme (ACE). Ang II, still considered the main effector of RAS was believed to act only as a circulating hormone via angiotensin receptors, AT1 and AT2. Since then, an expanded view of RAS has gradually emerged. Local tissue RAS systems have been identified in most organs. Recently, evidence for an intracellular RAS has been reported. The new expanded view of RAS therefore covers both endocrine, paracrine and intracrine functions. Other peptides of RAS have been shown to have biological actions; angiotensin 2,8 heptapeptide (Ang III) has actions similar to those of Ang II. Further, the angiotensin 3,8 hexapeptide (Ang IV) exerts its actions via insulin-regulated amino peptidase receptors. Finally, angiotensin 1,7 (Ang 1,7) acts via mas receptors. The discovery of another ACE2 was an important complement to this picture. The recent discovery of renin receptors has made our view of RAS unexpectedly complex and multilayered. The importance of RAS in cardiovascular disease has been demonstrated by the clinical benefits of ACE inhibitors and AT1 receptor blockers. Great expectations are now generated by the introduction of renin inhibitors. Indeed, RAS regulates much more and diverse physiological functions than previously believed. [source]

Molecular characterization, function and regulation of ammonium transporters (Amt) and ammonium-metabolizing enzymes (GS, NADP-GDH) in the ectomycorrhizal fungus Hebeloma cylindrosporum

MOLECULAR MICROBIOLOGY, Issue 2 2003
Arnaud Javelle
Summary External hyphae, which play a key role in nitrogen nutrition of trees, are considered as the absorbing structures of the ectomycorrhizal symbiosis. Here, we have cloned and characterized Hebeloma cylindrosporum AMT1, GLNA and GDHA genes, which encode a third ammonium transporter, a glutamine synthetase and an NADP-dependent glutamate dehydrogenase respectively. Amt1 can fully restore the pseudohyphal growth defect of a Saccharomyces cerevisiae mep2 mutant, and this is the first evidence that a heterologous member of the Mep/Amt family complements this dimorphic change defect. Dixon plots of the inhibition of methylamine uptake by ammonium indicate that Amt1 has a much higher affinity than the two previously characterized members (Amt2 and Amt3) of the Amt/Mep family in H. cylindrosporum. We also identified the intracellular nitrogen pool(s) responsible for the modulation of expression of AMT1, AMT2, AMT3, GDHA and GLNA. In response to exogenously supplied ammonium or glutamine, AMT1, AMT2 and GDHA were downregulated and, therefore, these genes are subjected to nitrogen repression in H. cylindrosporum. Exogenously supplied nitrate failed to induce a downregulation of the five mRNAs after transfer of mycelia from a N-starved condition. Our results demonstrate that glutamine is the main effector for AMT1 and AMT2 repression, whereas GDHA repression is controlled by intracellular ammonium, independently of the intracellular glutamine or glutamate concentration. Ammonium transport activity may be controlled by intracellular NH4+. AMT3 and GLNA are highly expressed but not highly regulated. A model for ammonium assimilation in H. cylindrosporum is presented. [source]

AT1 -receptor blockade and sympathetic neurotransmission in cardiovascular disease

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 5-6 2003
A. Nap
Summary 1 The present survey is dealing with the interactions between the renin,angiotensin,aldosterone system (RAAS) and the sympathetic nervous system (SNS) in various organs and tissues, with an emphasis on the angiotensin AT-receptors located at the sympathetic nerve endings. 2 Angiotensin II, the main effector of the RAAS is known to stimulate sympathetic nerve traffic and its sequelae in numerous organs and tissues, such as the central nervous system, the adrenal medulla, the sympathetic ganglia and the sympathetic nerve endings. These stimulatory effects are mediated by AT1 -receptors and counteracted by AT1 -receptor antagonists. 3 Sympatho-inhibition at the level of the sympathetic nerve ending appears to be a class effect of the AT1 -receptor blockers, mediated by presynaptic AT1 -receptors. With respect to the ratio pre-/postsynaptic AT1 -receptor antagonism important quantitative differences between the various compounds were found. 4 Both the pre- and postjunctional receptors at the sympathetic nerve endings belong to the AT1 -receptor population. However, the presynaptic receptors belong to the AT1B -subtype, whereas the postjunctional receptors probably belong to a different AT1 -receptor subpopulation. 5 Sympatho-inhibition is a class effect of the AT1 -receptor antagonists. In conditions in which the SNS plays a pathophysiological role, such as hypertension and congestive heart failure, this property may well be of therapeutic relevance. [source]

Specificity of the second messenger pathways involved in basic fibroblast growth factor-induced survival and neurite growth in chick ciliary ganglion neurons

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2009
Alessandra Gilardino
Abstract Basic fibroblast growth factor (bFGF) exerts multiple neurotrophic actions on cultured neurons from the ciliary ganglion of chick embryo, among them promotion of neuronal survival and of neurite outgrowth. To understand the specificity of the signal transduction cascades involved in the control of these processes, we used pharmacological inhibitors of the three main effectors known to act downstream of the bFGF receptor (FGFR): phospholipase C, (PLC,), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3-K). Neuronal survival was assessed at 24 and 48 hr; neurite growth was analyzed both on dissociated neurons and on explants of whole ganglia. Our data show that only the PI3-K pathway is involved in the survival-promoting effect of bFGF; on the other hand, all three effectors converge on the enhancement of neurite outgrowth, both on isolated neurons and in whole ganglia. © 2009 Wiley-Liss, Inc. [source]