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Spontaneous Release (spontaneous + release)
Selected AbstractsEvidence for Spontaneous Release of Acrylates from a Transition-Metal Complex Upon Coupling Ethene or Propene with a Carboxylic Moiety or CO2CHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2007Michele Aresta Prof. Abstract The development of a new synthetic approach to acrylates based on the formation of alkyl esters of acrylic acids has been studied. A preformed Pd,COOMe moiety is used as a model system to investigate the insertion of an olefin into the PdC bond. The fast elimination of acrylate is observed. Density functional calculations support the experimental findings and allow the characterization of transition states along the reaction pathway. The first example of olefin/CO2 coupling with facile release of ethyl acrylate is also presented. [source] Development of selective tolerance to interleukin-1, by human chondrocytes in vitro,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2002Greta M. Lee Interleukin-1 induces release of NO and PGE2 and production of matrix degrading enzymes in chondrocytes. In osteoarthritis (OA), IL-1 continually, or episodically, acts on chondrocytes in a paracrine and autocrine manner. Human chondrocytes in chondron pellet culture were treated chronically (up to 14 days) with IL-1,. Chondrons from OA articular cartilage were cultured for 3 weeks before treatment with IL-1, (0.05,10 ng/ml) for an additional 2 weeks. Spontaneous release of NO and IL-1, declined over the pretreatment period. In response to IL-1, (0.1 ng/ml), NO and PGE2 release was maximal on Day 2 or 3 and then declined to near basal level by Day 14. Synthesis was recovered by addition of 1 ng/ml IL-1, on Day 11. Expression of inducible nitric oxide synthase (iNOS), detected by immunofluorescence, was elevated on Day 2 and declined through Day 14, which coordinated with the pattern of NO release. On the other hand, IL-1,-induced MMP-13 synthesis was elevated on Day 3, declined on Day 5, and then increased again through Day 14. IL-1, increased glucose consumption and lactate production throughout the treatment. IL-1, stimulated proteoglycan degradation in the early days and inhibited proteoglycan synthesis through Day 14. Chondron pellet cultures from non-OA cartilage released the same amount of NO but produced less PGE2 and MMP-13 in response to IL-1, than OA cultures. Like the OA, IL-1,-induced NO and PGE2 release decreased over time. In conclusion, with prolonged exposure to IL-1,, human chondrocytes develop selective tolerance involving NO and PGE2 release but not MMP-13 production, metabolic activity, or matrix metabolism. © 2002 Wiley-Liss, Inc. [source] Activation of histaminergic H3 receptors in the rat basolateral amygdala improves expression of fear memory and enhances acetylcholine releaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2002Iacopo Cangioli Abstract The basolateral amygdala (BLA) is involved in learning that certain environmental cues predict threatening events. Several studies have shown that manipulation of neurotransmission within the BLA affects the expression of memory after fear conditioning. We previously demonstrated that blockade of histaminergic H3 receptors decreased spontaneous release of acetylcholine (ACh) from the BLA of freely moving rats, and impaired retention of fear memory. In the present study, we examined the effect of activating H3 receptors within the BLA on both ACh release and expression of fear memory. Using the microdialysis technique in freely moving rats, we found that the histaminergic H3 agonists R-,-methylhistamine (RAMH) and immepip, directly administered into the BLA, augmented spontaneous release of ACh in a similar manner. Levels of ACh returned to baseline on perfusion with control medium. Rats receiving intra-BLA, bilateral injections of the H3 agonists at doses similar to those enhancing ACh spontaneous release, immediately after contextual fear conditioning, showed stronger memory for the context,footshock association, as demonstrated by longer freezing assessed at retention testing performed 72 h later. Post-training, bilateral injections of 15 ng oxotremorine also had a similar effect on memory retention, supporting the involvement of the cholinergic system. Thus, our results further support a physiological role for synaptically released histamine, that in addition to affecting cholinergic transmission in the amygdala, modulates consolidation of fear memories [source] Endogenous histamine in the medial septum,diagonal band complex increases the release of acetylcholine from the hippocampus: a dual-probe microdialysis study in the freely moving ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002Lucia Bacciottini Abstract The effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c-fos in the medial septum,diagonal band (MSA-DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA-DB neurons, we used the dual-probe microdialysis technique to apply drugs to the MSA-DB and record the induced effects in the projection area. Perfusion of MSA-DB with high-KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra-MSA-DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA-DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA-DB, increased the release of hippocampal ACh, whereas R-,-methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA-DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c-fos immunoreactivity were significantly more numerous in ciproxifan- or thioperamide-treated rats than in controls, although no colocalization of anti-c-fos and anti-ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus. [source] Histamine H3 receptor-mediated impairment of contextual fear conditioning and in-vivo inhibition of cholinergic transmission in the rat basolateral amygdalaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001M. Beatrice Passani Abstract We investigated the effects of agents acting at histamine receptors on both, spontaneous release of ACh from the basolateral amygdala (BLA) of freely moving rats, and fear conditioning. Extensive evidence suggests that the effects of histamine on cognition might be explained by the modulation of cholinergic systems. Using the microdialysis technique in freely moving rats, we demonstrated that perfusion of the BLA with histaminergic compounds modulates the spontaneous release of ACh. The addition of 100 mm KCl to the perfusion medium strongly stimulated ACh release, whereas, 0.5 µm tetrodotoxin (TTX) inhibited spontaneous ACh release by more than 50%. Histaminergic H3 antagonists (ciproxifan, clobenpropit and thioperamide), directly administered to the BLA, decreased ACh spontaneous release, an effect fully antagonized by the simultaneous perfusion of the BLA with cimetidine, an H2 antagonist. Local administration of cimetidine alone increased ACh spontaneous release slightly, but significantly. Conversely, the administration of H1 antagonists failed to alter ACh spontaneous release. Rats receiving intra-BLA, bilateral injections of the H3 antagonists at doses similar to those inhibiting ACh spontaneous release, immediately after contextual fear conditioning, showed memory consolidation impairment of contextual fear conditioning. Post-training, bilateral injections of 50 µg scopolamine also had an adverse effect on memory retention. These observations provide the first evidence that histamine receptors are involved in the modulation of cholinergic tone in the amygdala and in the consolidation of fear conditioning. [source] SIGIRR/TIR-8 is an inhibitor of toll-like receptor signaling in primary human cells and regulates inflammation in models of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 8 2010Stefan K. Drexler Objective Single-immunoglobulin interleukin-1 receptor,related (SIGIRR), which is also known as Toll/interleukin-1 receptor 8 (TIR-8), is a member of the TIR domain,containing family of receptors and was first characterized as an inhibitor of interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) signaling. In the Dextran sulfate sodium,induced colitis model, SIGIRR,/, mice were shown to have increased inflammation and to be more susceptible to endotoxin challenge. Increasing evidence implicates TLR and IL-1R signaling in the pathology of rheumatoid arthritis (RA). Therefore, the purpose of this study was to investigate the involvement of SIGIRR in regulating inflammation in disease-relevant models. Methods Primary human monocyte-derived macrophages and dendritic cells (DCs) were used to overexpress SIGIRR as well as to knock down endogenously expressed SIGIRR using small interfering RNAs. SIGIRR was also overexpressed in synovial cells derived from RA patients. To investigate the role of SIGIRR in vivo, zymosan-induced arthritis (ZIA) and collagen antibody,induced arthritis (CAIA) were induced in SIGIRR-knockout mice. Results SIGIRR overexpression inhibited TLR-induced cytokine production in macrophages and DCs, while SIGIRR knockdown resulted in increased cytokine production following TLR stimulation. Moreover, SIGIRR overexpression inhibited the spontaneous release of cytokines by human RA synovial cells. The role of SIGIRR as an inhibitor of inflammation was confirmed in vivo, since SIGIRR,/, mice developed a more severe disease in both the ZIA and CAIA models. Conclusion Our study is the first to show the expression pattern and function of SIGIRR in primary human cells. Furthermore, this investigation defines the role of SIGIRR in disease-relevant cell types and demonstrates that SIGIRR is a potential therapeutic target for RA. [source] Role of sarcoplasmic reticulum in control of membrane potential and nitrergic response in opossum lower esophageal sphincterBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2003Yong Zhang We previously demonstrated that a balance of Ca2+ -activated Cl, current (ICl(Ca)) and K+ current activity sets the resting membrane potential of opossum lower esophageal sphincter (LES) circular smooth muscle at ,,41 mV, which leads to continuous spike-like action potentials and the generation of basal tone. Ionic mechanisms underlying this basal ICl(Ca) activity and its nitrergic regulation remain unclear. Recent studies suggest that spontaneous Ca2+ release from sarcoplasmic reticulum (SR) and myosin light chain kinase (MLCK) play important roles. The current study investigated this possibility. Conventional intracellular recordings were performed on circular smooth muscle of opossum LES. Nerve responses were evoked by electrical square wave pulses of 0.5 ms duration at 20 Hz. In the presence of nifedipine (1 ,M), substance P (1 ,M), atropine (3 ,M) and guanethidine (3 ,M), intracellular recordings demonstrated a resting membrane potential (MP) of ,38.1±0.7 mV (n=25) with spontaneous membrane potential fluctuations (MPfs) of 1,3 mV. Four pulses of nerve stimulation induced slow inhibitory junction potentials (sIJPs) with an amplitude of 6.1±0.3 mV and a half-amplitude duration of 1926±147 ms (n=25). 1H -[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a specific guanylyl cyclase inhibitor, abolished sIJPs, but had no effects on MPfs. Caffeine, a ryanodine receptor agonist, hyperpolarized MP and abolished sIJPs and MPfs. Ryanodine (20 ,M) inhibited the sIJP and induced biphasic effects on MP, an initial small hyperpolarization followed by a large depolarization. sIJPs and MPfs were also inhibited by cyclopiazonic acid, an SR Ca2+ ATPase inhibitor. Specific ICl(Ca) and MLCK inhibitors hyperpolarized the MP and inhibited MPfs and sIJPs. These data suggest that (1) spontaneous release of Ca2+ from the SR activates ICl(Ca), which in turn contributes to resting membrane potential; (2) MLCK is involved in activation of ICl(Ca); (3) inhibition of ICl(Ca) is likely to underlie sIJPs induced by nitrergic innervation. British Journal of Pharmacology (2003) 140, 1097,1107. doi:10.1038/sj.bjp.0705537 [source] In vivo Mutational Analysis of the Mupirocin Gene Cluster Reveals Labile Points in the Biosynthetic Pathway: the "Leaky Hosepipe" MechanismCHEMBIOCHEM, Issue 9 2008Ji'en Wu Dr. Abstract A common feature of the mupirocin and other gene clusters of the AT-less polyketide synthase (PKS) family of metabolites is the introduction of carbon branches by a gene cassette that contains a ,-hydroxy-,-methylglutaryl CoA synthase (HMC) homologue and acyl carrier protein (ACP), ketosynthase (KS) and two crotonase superfamily homologues. In vivo studies of Pseudomonas fluorescens strains in which any of these components have been mutated reveal a common phenotype in which the two major isolable metabolites are the truncated hexaketide mupirocin H and the tetraketide mupiric acid. The structure of the latter has been confirmed by stereoselective synthesis. Mupiric acid is also the major metabolite arising from inactivation of the ketoreductase (KR) domain of module 4 of the modular PKS. A number of other mutations in the tailoring region of the mupirocin gene cluster also result in production of both mupirocin H and mupiric acid. To explain this common phenotype we propose a mechanistic rationale in which both mupirocin H and mupiric acid represent the products of selective and spontaneous release from labile points in the pathway that occur at significant levels when mutations block the pathway either close to or distant from the labile points. [source] Spontaneous electrical and Ca2+ signals in the mouse renal pelvis that drive pyeloureteric peristalsisCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2010Richard J Lang Summary 1.,Peristalsis in the smooth muscle cell (SMC) wall of the pyeloureteric system is unique in physiology in that the primary pacemaker resides in a population of atypical SMCs situated near the border of the renal papilla. 2.,Atypical SMCs display high-frequency Ca2+ transients upon the spontaneous release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-dependent stores that trigger cation-selective spontaneous transient depolarizations (STDs). In the presence of nifedipine, these Ca2+ transients and STDs seldom propagate > 100 ,m. Synchronization of STDs in neighbouring atypical SMCs into an electrical signal that can trigger action potential discharge and contraction in the typical SMC layer involves a coupled oscillator mechanism dependent on Ca2+ entry through L-type voltage-operated Ca2+ channels. 3.,A population of spindle- or stellate-shaped cells, immunopositive for the tyrosine receptor kinase kit, is sparsely distributed throughout the pyeloureteric system. In addition, Ca2+ transients and action potentials of long duration occurring at low frequencies have been recorded in a population of fusiform cells, which we have termed interstitial cells of Cajal (ICC)-like cells. 4.,The electrical and Ca2+ signals in ICC-like cells are abolished upon blockade of Ca2+ release from either IP3 - or ryanodine-dependent Ca2+ stores. However, the spontaneous Ca2+ signals in atypical SMCs or ICC-like cells are little affected in W/W,v transgenic mice, which have extensive lesions of their intestinal ICC networks. 5.,In summary, we have developed a model of pyeloureteric pacemaking in which atypical SMCs are indeed the primary pacemakers, but the function of ICC-like cells has yet to be determined. [source] | ||||||||||||||||