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Receptor Signalling Pathway (receptor + signalling_pathway)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Erythropoietin protects the in vitro blood,brain barrier against VEGF-induced permeability

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2003
Ofelia María Martínez-Estrada
Abstract The blood,brain barrier (BBB) ensures the homeostasis of the brain microenvironment, mostly through complex tight junctions between brain endothelial cells that prevent the passage of hydrophilic molecules from blood to brain and vice versa. A recent study has shown in vivo that systemic administration of erythropoietin (Epo) protects against brain injury. Using an in vitro model of the bovine BBB, we observed that the expression of the Epo receptor is modulated by its ligand and hypoxic stimuli such as vascular endothelial growth factor (VEGF) treatment. In addition, Epo protects against the VEGF-induced permeability of the BBB, decreases the levels of endothelial nitric oxide synthase and restores junction proteins. The kinetic transport experiments revealed the capacity of Epo to cross the in vitro BBB in a saturable and specific way. Our results suggest a new mechanism for Epo-induced neuroprotection, in which circulating Epo controls and maintains the BBB through an Epo receptor signalling pathway and the re-establishment of cell junctions. [source]

Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF-I receptor signalling pathway

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009
Li Xu
Background and purpose:, We have shown that ginsenoside Rg1 is a novel class of potent phytoestrogen and activates insulin-like growth factor-I receptor (IGF-IR) signalling pathway in human breast cancer MCF-7 cells. The present study tested the hypothesis that the neuroprotective actions of Rg1 involved activation of the IGF-IR signalling pathway in a rat model of Parkinson's disease, induced by 6-hydroxydopamine (6-OHDA). Experimental approach:, Ovariectomized rats were infused unilaterally with 6-OHDA into the medial forebrain bundle to lesion the nigrostriatal dopamine pathway and treated with Rg1 (1.5 h after 6-OHDA injections) in the absence or presence of the IGF-IR antagonist JB-1 (1 h before Rg1 injections). The rotational behaviour induced by apomorphine and the dopamine content in the striatum were studied. Protein and gene expression of tyrosine hydroxylase, dopamine transporter and Bcl-2 in the substantia nigra were also determined. Key results:, Rg1 treatment ameliorated the rotational behaviour induced by apomorphine in our model of nigrostriatal injury. This effect was partly blocked by JB-1. 6-OHDA significantly decreased the dopamine content of the striatum and treatment with Rg1 reversed this decrease. Treatment with Rg1 of 6-OHDA-lesioned rats reduced neurotoxicity, as measured by tyrosine hydroxylase, dopamine transporter and Bcl-2 protein and gene level in the substantia nigra. These effects were abolished by JB-1. Conclusions and implications:, These data provide the first evidence that Rg1 has neuroprotective effects on dopaminergic neurons in the 6-OHDA model of nigrostriatal injury and its actions might involve activation of the IGF-IR signalling pathway. [source]

The chemokine receptor CCX-CKR mediates effective scavenging of CCL19 in vitro

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006
Iain Comerford
Abstract The chemokines CCL19, CCL21 and CCL25, by signalling through the receptors CCR7 or CCR9, play critical roles in leukocyte homing. They also bind another heptahelical surface protein, CCX-CKR. CCX-CKR cannot couple to typical chemokine receptor signalling pathways or mediate chemotaxis, and its function remains unclear. We have proposed that it controls chemokine bioavailability. Here, using transfected HEK293 cells, we have shown that both CCX-CKR and CCR7 mediate rapid CCL19 internalisation upon initial chemokine exposure. However, internalised CCL19 was more efficiently retained and degraded after uptake via CCX-CKR. More importantly, CCR7 rapidly became refractory for CCL19 uptake, but the sequestration activity of CCX-CKR was enhanced. These properties endowed CCX-CKR with an impressive ability to mediate progressive sequestration and degradation of large quantities of CCL19, and conversely, prevented CCR7-expressing cells from extensively altering their chemokine environment. These differences may be linked to the routes of endocytosis used by these receptors. CCX-CKR, unlike CCR7, was not critically dependent on ,-arrestins or clathrin-coated pits. However, over-expression of caveolin-1, which stabilises caveolae, blocked CCL19 uptake by CCX-CKR while having no impact on other chemokine receptors, including CCR7. These data predict that CCX-CKR scavenges extracellular chemokines in vivo to modify responses through CCR7. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636327 [source]

Brain superoxide as a key regulator of the cardiovascular response to emotional stress in rabbits

EXPERIMENTAL PHYSIOLOGY, Issue 3 2007
Dmitry N. Mayorov
Cardiovascular reactivity, an abrupt increase in blood pressure and heart rate in response to emotional stress, is a risk factor for hypertension and heart disease. Brain angiotensin II (Ang II) type 1 (AT1) receptor is increasingly recognized as an important regulator of cardiovascular reactivity. Given that a wide variety of AT1 receptor signalling pathways exists in neurones, the precise molecular mechanisms that underlie central cardiovascular actions of Ang II during emotional stress are yet to be determined. Growing evidence, however, indicates that reactive oxygen species, and in particular superoxide (·O2,), are important intracellular messengers of many actions of brain Ang II. In particular, studies employing microinjection of ·O2, scavengers directly into the rostral ventrolateral medulla (RVLM) and dorsomedial hypothalamus of rabbits have shown that the activation of AT1 receptor,·O2, signalling is required for full manifestation of the cardiovascular response to emotional stress. This role of ·O2, appears to be highly specific, because ·O2, scavengers in the RVLM do not alter the sympathoexcitatory response to baroreceptor unloading or sciatic nerve stimulation. The subcellular mechanisms for the stress-induced ·O2, production are likely to include the activation of NADPH oxidase and are essentially independent of nitric oxide. This review summarizes current knowledge of redox-sensitive signalling mechanisms in the brain that regulate cardiovascular effects of stress. Additionally, it presents initial evidence that ·O2, may be less important in the activation of central pressor pathways mediating cardiovascular arousal associated with appetitive events, such as food anticipation and feeding. [source]