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Subsequent Stimulation (subsequent + stimulation)
Selected AbstractsGlial cell-derived glutamate mediates autocrine cell volume regulation in the retina: activation by VEGFJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Antje Wurm Abstract Astroglial cells are a source for gliotransmitters such as glutamate and ATP. We demonstrate here that gliotransmitters have autocrine functions in the regulation of cellular volume. Hypoosmotic stress in the presence of inflammatory mediators or oxidative stress, and during blockade or down-regulation of potassium channels, induces swelling of retinal glial cells. Vascular endothelial growth factor inhibits the osmotic swelling of glial cells in retinal slices or isolated cells. This effect was mediated by a kinase domain region/flk-1 receptor-evoked calcium dependent release of glutamate from glial cells, and subsequent stimulation of glial group I/II metabotropic glutamate receptors. Activation of kinase domain region/flk-1 or glutamate receptors evoked an autocrine swelling-inhibitory purinergic signaling cascade that was calcium-independent. This cascade involved the release of ATP and adenosine, and the activation of purinergic P2Y1 and adenosine A1 receptors, resulting in the opening of potassium and chloride channels and inhibition of cellular swelling. The glutamatergic-purinergic regulation of the glial cell volume may be functionally important in the homeostasis of the extracellular space volume during intense neuronal activation which is associated with a swelling of neuronal cell structures in the retina. However, glial cell-derived glutamate may also contribute to the swelling of activated neurons since metabolic poisoning of glial cells by iodoacetate inhibits the neuronal cell swelling mediated by activation of ionotropic glutamate receptors. [source] Cannabinoid,vanilloid receptor interactions in pain signalingJOURNAL OF NEUROCHEMISTRY, Issue 2003V. Di Marzo Agents that activate cannabinoid CB1 receptors for marijuana's active principal, THC, or vanilloid VR1 receptors for red chilli peppers' pungent ingredient, capsaicin, modulate pain perception. Stimulation of presynaptic CB1 leads to inhibition of glutamate release in the spinal cord, whereas VR1 stimulation causes release of substance P and CGRP from DRG neurons. VR1 undergoes rapid desensitization by its agonists, which makes VR1-expressing neurons insensitive to subsequent stimulation and results in analgesia. Thus, both CB1 and VR1, which are coexpressed in several spinal and DRG neurons, are targets for analgesic drug development. CB1 and VR1 also share endogenous agonists, namely anandamide, NADA and some of their analogs, and may be regarded as metabotropic and ionotropic receptors for the same family of mediators, with opposing roles in pain perception. The development of ,hybrid' CB1/VR1 agonists as potent analgesics and the functional relationships between CB1 and VR1 in sensory neurons will be discussed. [source] Crystallization and preliminary X-ray crystallographic studies of the Z-DNA-binding domain of a PKR-like kinase (PKZ) in complex with Z-DNAACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2009Doyoun Kim PKZ, a PKR-like eIF2, kinase, consists of a Z-DNA-specific binding domain (Z,) and an eIF2, kinase domain. The kinase activity of PKZ is modulated by the binding of Z, to Z-DNA. The mechanisms underlying Z-DNA binding and the subsequent stimulation of PKZ raise intriguing questions. Interestingly, the Z-DNA-binding domain of PKZ from goldfish (Carassius auratus; caZ,PKZ) shows limited sequence homology to other canonical Z, domains, suggesting that it may have a distinct Z-DNA-recognition mode. In this study, the Z-DNA-binding activity and stoichiometry of caZ,PKZ were confirmed using circular dichroism (CD). In addition, preliminary X-ray studies of the caZ,PKZ,Z-DNA complex are reported as the first step in the determination of its three-dimensional structure. Bacterially expressed recombinant caZ,PKZ was purified and crystallized with Z-DNA at 295,K using the microbatch method. X-ray diffraction data were collected to 1.7,Å resolution with an Rmerge of 7.4%. The crystals belonged to the monoclinic space group C2, with unit-cell parameters a = 55.54, b = 49.93, c = 29.44,Å, , = 96.5°. Structural analysis of caZ,PKZ,Z-DNA will reveal the binding mode of caZ,PKZ to Z-DNA and its relevance to other Z-DNA-binding proteins. [source] Intermolecular cross-talk between the prostaglandin E2 receptor (EP)3 subtype and thromboxane A2 receptor signalling in human erythroleukaemic cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009Helen M Reid Background and purpose:, In previous studies investigating cross-talk of signalling between prostaglandin (PG)E2 receptor (EP) and the TP, and TP, isoforms of the human thromboxane (TX)A2 receptor (TP), 17-phenyl trinor PGE2 -induced desensitization of TP receptor signalling through activation of the AH6809 and SC19220-sensitive EP1 subtype of the EP receptor family, in a cell-specific manner. Here, we sought to further investigate that cross-talk in human erythroleukaemic (HEL) 92.1.7 cells. Experimental approach:, Specificity of 17-phenyl trinor PGE2 signalling and its possible cross-talk with signalling by TP,/TP, receptors endogenously expressed in HEL cells was examined through assessment of agonist-induced inositol 1,4,5-trisphosphate (IP)3 generation and intracellular calcium ([Ca2+]i) mobilization. Key results:, While 17-Phenyl trinor PGE2 led to activation of phospholipase (PL)C, to yield increases in IP3 generation and [Ca2+]i, it did not desensitize but rather augmented that signalling in response to subsequent stimulation with the TXA2 mimetic U46619. Furthermore, the augmentation was reciprocal. Signalling by 17-phenyl trinor PGE2 was found to occur through AH6809- and SC19920-insensitive, Pertussis toxin-sensitive, Gi/G,, -dependent activation of PLC,. Further pharmacological investigation using selective EP receptor subtype agonists and antagonists confirmed that 17-phenyl trinor PGE2 -mediated signalling and reciprocal cross-talk with the TP receptors occurred through the EP3, rather than the EP1, EP2 or EP4 receptor subtype in HEL cells. Conclusions and Implications:, The EP1 and EP3 subtypes of the EP receptor family mediated intermolecular cross-talk to differentially regulate TP receptor-mediated signalling whereby activation of EP1 receptors impaired or desensitized, while that of EP3 receptors augmented signalling through TP,/TP, receptors, in a cell type-specific manner. [source] Antagonists of ionotropic ,-aminobutyric acid receptors impair the NiCl2 -mediated stimulation of the electroretinogram b-wave amplitude from the isolated superfused vertebrate retinaACTA OPHTHALMOLOGICA, Issue 8 2009Siarhei A Siapich Abstract. Purpose:, NiCl2 (15 ,M) stimulates the electroretinogram (ERG) b-wave amplitude of vertebrate retina up to 1.5-fold through its blocking of E/R-type voltage-gated Ca2+ channels. Assuming that such an increase is mediated by blocking the release of the inhibitory neurotransmitter ,-aminobutyric acid (GABA) via ionotropic GABA receptors, we tested the effect of both GABA itself and GABA-receptor antagonists such as (,)bicuculline (1.51-fold increase) and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA; 1.46-fold increase) on the b-wave amplitude. Methods:, Recording of the transretinal potentials from the isolated bovine retina. Results:, GABA (100 ,M) reduced the b-wave amplitude only when NiCl2 (15 ,M) was applied first. Each antagonist applied on its own stimulated the b-wave amplitude only partially: subsequent NiCl2 superfusion caused a small but additional increase, leading to a 1.69- and a 1.88-fold total increase of the amplitude by Ni2+ plus (,)bicuculline or Ni2+ plus TPMPA, respectively. Only the application of both antagonists in combination, before superfusing low NiCl2 (15 ,M), completely prevented subsequent stimulation by NiCl2 with a similar 1.90-fold total increase of b-wave amplitude. Those retina segments that did not respond to NiCl2 could not be stimulated by (,)bicuculline and vice versa. Conclusion:, The stimulatory effect of NiCl2 on the ERG b-wave amplitude is mainly, but not only, mediated by a NiCl2 -sensitive, Cav2.3-triggered GABA release acting through ionotropic GABA-A and GABA-C receptors. [source] | ||||||||||