Home About us Contact
|
Home About us Contact | ||
|
|
||
Receptors Other (receptor + other)
Selected AbstractsConduction block and glial injury induced in developing central white matter by glycine, GABA, noradrenalin, or nicotine, studied in isolated neonatal rat optic nerveGLIA, Issue 11 2009Stavros Constantinou Abstract The damaging effects of excessive glutamate receptor activation have been highlighted recently during injury in developing central white matter. We have examined the effects of acute exposure to four other neurotransmitters that have known actions on white matter. Eighty minutes of Glycine or GABA-A receptor activation produced a significant fall in the compound action potential recorded from isolated post-natal day 10 rat optic nerve. This effect was largely reversed upon washout. Nicotinic acetylcholine receptor (nAChR) or adrenoreceptor activation with noradrenalin resulted in an ,35% block of the action potential that did not reverse during a 30-min washout period. While the effect of nAChR activation was blocked by a nAChR antagonist, the effect of noradrenalin was not ablated by ,- or ,-adrenoreceptor blockers applied alone or in combination. In the absence of noradrenalin, co-perfusion with ,- and ,-adrenoreceptor blockers resulted in nonreversible nerve failure indicating that tonic adrenoreceptor activation is required for nerve viability, while overactivation of these receptors is also damaging. Nerves exposed to nAChR + adrenoreceptor activation showed no axon pathology but had extensive glial injury revealed by ultrastructural analysis. Oligodendroglia exhibited regions of membrane vacuolization while profound changes were evident in astrocytes and included the presence of swollen and expanded mitochondria, vacuolization, cell processes disintegration, and membrane breakdown. Blinded assessment revealed higher levels of astrocyte injury than oligodendroglial injury. The findings show that overactivation of neurotransmitter receptors other than those for glutamate can produce extensive injury to developing white matter, a phenomenon that may be clinically significant. © 2009 Wiley-Liss, Inc. [source] Inherited disorders of human Toll-like receptor signaling: immunological implicationsIMMUNOLOGICAL REVIEWS, Issue 1 2005Cheng-Lung Ku Summary:,In vitro nine of 10 known human Toll-like receptors (TLRs) are engaged by well-defined chemical agonists that mimic microbial compounds, raising the possibility that human TLRs play a critical role in protective immunity in vivo. We thus review here the recently described human primary immunodeficiencies caused by germline mutations in genes encoding molecules involved in cell signaling downstream from TLRs. Subjects with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) carry either X-linked recessive hypomorphic mutations in NEMO or autosomal dominant hypermorphic mutations in IKBA. Their cells show a broad defect in nuclear factor-,B (NF-,B) activation, with an impaired, but not abolished response to a large variety of stimuli including TLR agonists. EDA-ID patients show developmental anomalies of skin appendages and a broad spectrum of infectious diseases. Patients with autosomal recessive amorphic mutations in IRAK4 present a purely immunological syndrome and more restricted defects, with specific impairment of the Toll and interleukin-1 receptor (TIR),interleukin-1 receptor-associated kinase (IRAK) signaling pathway. In these subjects, the NF-,B- and mitogen-activated protein kinase-mediated induction of inflammatory cytokines in response to TIR agonists is impaired. The patients present a narrow range of pyogenic bacterial infections that become increasingly rare with age. Altogether, these data suggest that human TLRs play a critical role in host defense. However, they do not provide compelling evidence, as even the infectious phenotype of patients with mutations in IRAK4 may result from impaired signaling via receptors other than TLRs. Paradoxically, these experiments of nature raise the possibility that the entire set of human TLRs is largely redundant in protective immunity in vivo. [source] Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptorJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Bernardo Nuche-Berenguer Glucagon-like peptide 1 (GLP-1) controls glucose metabolism in extrapancreatic tissues through receptors other than the pancreatic cAMP-linked GLP-1 receptor; also, GLP-1 induces an insulin- and PTH-independent bone anabolic action in insulin-resistant and type-2 diabetic rats. Here we searched for the presence and characteristics of GLP-1 receptors in osteoblastic MC3T3-E1 cells. [125I]-GLP-1 specific binding to MC3T3-E1 cells was time- and temperature-dependent, reaching maximal value at 30,min at 25°C; in these conditions, [125I]-GLP-1 binding was dissociable, and displaced by GLP-1, partially by GLP-2, but not by exendin-4 (Ex-4), exendin-9 (Ex-9), glucagon or insulin; Scatchard analysis of the unlabeled GLP-1 data showed high and low affinity binding sites; cross-linking of GLP-1 binding revealed an estimated 70,kDa band, almost undetectable in the presence of 10,6,M GLP-1. GLP-1, Ex-9, insulin or glucagon failed to modify cellular cAMP content, while GLP-2 and Ex-4 increased it. However, GLP-1 induced an immediate hydrolysis of glycosylphosphatidylinositols (GPIs) generating short-lived inositolphosphoglycans (IPGs), and an increase in phosphatidylinositol-3 kinase (PI3K) and mitogen activated protein kinase (MAPK) activities; Ex-4 also affected GPIs, but its action was delayed with respect to that of GLP-1. This incretin was found to decrease Runx2 but increased osteocalcin gene expression, without affecting that of osteoprotegerin or the canonical Wnt pathway activity in MC3T3-E1 cells which do not express the pancreatic GLP-1 receptor. Our data demonstrate for the first time that GLP-1 can directly and functionally interact with osteoblastic cells, possibly through a GPI/IPG-coupled receptor. J. Cell. Physiol. 225: 585,592, 2010. © 2010 Wiley-Liss, Inc. [source] Crystallization and preliminary X-ray diffraction characterization of an essential protein from Xanthomonas campestris that contains a noncanonical PilZ signature motif yet is critical for pathogenicityACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 10 2009Tso-Ning Li Recent studies have identified c-di-GMP as a novel secondary messenger molecule that is heavily involved in regulating bacterial biofilm formation, motility, production of pathogenicity factors etc. PilZ domain-containing proteins have been suggested and subsequently proved to be the c-di-GMP receptor. However, considering the diverse biological functions exhibited by c-di-GMP, it may be that receptors other than the PilZ domain exist. An essential protein from the plant pathogen Xanthomonas campestris pv. campestris (Xcc) that contains a noncanonical PilZ signature motif yet is critical for Xcc pathogenicity has been cloned, purified and crystallized. Detailed characterization of this protein may reveal an alternative binding mode of c-di-GMP and allow a more thorough understanding of how c-di-GMP exhibits its diverse effects. [source] Microreview: Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathwaysCELLULAR MICROBIOLOGY, Issue 10 2005Oren Froy Summary The immune system consists of innate and adaptive immune responses. The innate immune system confers non-specific protection against a large number of pathogens, hence, serving as the first line of defence. The innate immune system utilizes Toll-like receptors (TLRs) to recognize and bind pathogen-associated molecular patterns (PAMPs). Binding of PAMPs leads to TLR activation, which, in turn, initiates MAPK- or NF-,B-dependent cascades that culminate in a proinflammatory response. This response involves the secretion of cytokines, chemokines and broad-spectrum antibacterial substances, such as defensins. Increased defensin synthesis is also mediated by the activation of receptors other than TLRs, such as NOD2, IL-17R and PAR-2. This review summarizes the recently characterized signalling pathways leading to increased defensin synthesis as well as the pathway by which defensins activate TLRs on immature dendritic and memory T cells. Thus, not only do defensins eliminate pathogens, but they also recruit the adaptive immune system in instances of infection and/or inflammation. [source] | ||||||||||