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Like Receptors (like + receptor)
Selected AbstractsThe role of calcium on protein secretion of the albumen gland in Helisoma duryi (Gastropoda)INVERTEBRATE BIOLOGY, Issue 4 2004Lana Kiehn Abstract. The albumen gland of the freshwater pulmonate snail Helisoma duryi produces and secretes the perivitelline fluid, which coats fertilized eggs and provides nutrients to the developing embryos. It is known that perivitelline fluid secretion is stimulated by dopamine through the activation of a dopamine D1 -like receptor, which in turn stimulates cAMP production leading to the secretion of perivitelline fluid. This paper examines the glandular release of perivitelline fluid and provides evidence for the role of Ca2+ in the regulated secretion of perivitelline fluid based on protein secretion experiments and inositol 1,4,5-trisphosphate assays. Dopamine-stimulated protein secretion by the albumen gland is reduced in Ca2+ -free medium or in the presence of plasma membrane Ca2+ channel blockers, although the Ca2+ channel subtype involved is unclear. In addition, dopamine-stimulated protein secretion does not directly involve phospholipase C-generated signaling pathways and Ca2+ release from intracellular stores. Sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase inhibitors had little effect on protein secretion when applied alone; however, they potentiated dopamine-stimulated protein secretion. Dantrolene, an inhibitor of ryanodine receptors, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride, a nonspecific inhibitor of intracellular Ca2+ channels, and 2-aminoethyldiphenylborate, an inhibitor of inositol 1,4,5-trisphosphate receptors, did not suppress protein secretion, suggesting Ca2+ release from internal stores does not directly regulate protein secretion. Thus, the influx of Ca2+ from the extracellular space appears to be the major pathway mediating protein secretion by the albumen gland. The results are discussed with respect to the role of Ca2+ in controlling exocytosis of proteins from the albumen gland secretory cells. [source] The GABAergic-like system in the marine demosponge Chondrilla nuculaMICROSCOPY RESEARCH AND TECHNIQUE, Issue 11 2007Paola Ramoino Abstract Gamma-amino butyric acid (GABA) is believed to be the principal inhibitory neurotransmitter in the mammalian central nervous system, a function that has been extended to a number of invertebrate systems. The presence of GABA in the marine demosponge Chondrilla nucula was verified using immunofluorescence detection and high-pressure liquid chromatography. A strong GABA-like immunoreactivity (IR) was found associated with choanocytes, exopinacocytes, endopinacocytes lining inhalant, and exhalant canals, as well as in archaeocytes scattered in the mesohyl. The capacity to synthesize GABA from glutamate and to transport it into the vesicles was confirmed by the presence in C. nucula of glutamate decarboxylase (GAD) and vesicular GABA transporters (vGATs), respectively. GAD-like and vGAT-like IR show the same distribution as GABA-like IR. Supporting the similarity between sponge and mammalian proteins, bands with an apparent molecular weight of about 65,67 kDa and 57 kDa were detected using antibodies raised against mammalian GAD and vGAT, respectively. A functional metabotropic GABAB -like receptor is also present in C. nucula. Indeed, both GABAB R1 and R2 isoforms were detected by immunoblot and immunofluorescence. Also in this case, IR was found in choanocytes, exopinacocytes, and endopinacocytes. The content of GABA in C. nucula amounts to 1225.75 ± 79 pmol/mg proteins and GABA is released into the medium when sponge cells are depolarized. In conclusion, this study is the first indication of the existence of the GABA biosynthetic enzyme GAD and of the GABA transporter vGAT in sponges, as well as the first demonstration that the neurotransmitter GABA is released extracellularly. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source] Noncompetitive antagonism of BIBN4096BS on CGRP-induced responses in human subcutaneous arteriesBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2004Majid Sheykhzade We investigated the antagonistic effect of 1-piperidinecarboxamide, N -[2-[[5amino-l-[[4-(4-pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS) on the calcitonin gene-related peptide (CGRP)-induced responses by using isometric myograph and FURA-2 technique in human subcutaneous arteries removed in association with abdominal surgery. BIBN4096BS, at the concentration of 1 pM, had no significant effect on the CGRP-induced relaxation in these vessels. At the concentration of 10 pM, BIBN4096BS had a competitive antagonistic-like behaviour characterized by parallel rightward shift in the log CGRP concentration-tension curve with no depression of the Emax. At the higher concentrations (0.1 and 1 nM), BIBN4096BS had a concentration-dependent noncompetitive antagonistic effect on the CGRP-induced responses. The efficacy and potency of CGRP was significantly greater in the smaller (lumen diameter ,200 ,m) human subcutaneous arteries compared to the larger ones. The apparent agonist equilibrium dissociation constant, KA, for CGRP1 receptors in the human subcutaneous arteries was approximately 1 nM. Analysis of the relationship between receptor occupancy and response to CGRP indicates that the receptor reserve is relatively small. Using reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of mRNA sequences encoding the calcitonin receptor-like receptor, receptor activity modifying protein (RAMP1, RAMP2, RAMP3) and receptor component protein were demonstrated in human subcutaneous arteries, indicating the presence of CGRP1 -like receptor and the necessary component for the receptor activation. In conclusion, the inhibitory action of BIBN4096BS at the low concentration (10 pM) on the CGRP-tension curve (but not intracellular calcium concentration ([Ca2+]i) resembles what is seen with a reversible competitive antagonist. However, at the higher concentrations (0.1 and 1 nM), BIBN4096BS acts as a selective noncompetitive inhibitor at CGRP1 receptors in human subcutaneous arteries. British Journal of Pharmacology (2004) 143, 1066,1073. doi:10.1038/sj.bjp.0705967 [source] Nucleotide-induced Ca2+ signaling in sustentacular supporting cells of the olfactory epitheliumGLIA, Issue 15 2008Thomas Hassenklöver Abstract Extracellular purines and pyrimidines are important signaling molecules acting via purinergic cell-surface receptors in neurons, glia, and glia-like cells such as sustentacular supporting cells (SCs) of the olfactory epithelium (OE). Here, we thoroughly characterize ATP-induced responses in SCs of the OE using functional Ca2+ imaging. The initial ATP-induced increase of the intracellular Ca2+ concentration [Ca2+]i always occurred in the apical part of SCs and subsequently propagated toward the basal lamina, indicating the occurrence of purinergic receptors in the apical part of SCs. The mean propagation velocity of the Ca2+ signal within SCs was 17.10 ± 1.02 ,m/s. ATP evoked increases in [Ca2+]i in both the presence and absence of extracellular Ca2+. Depletion of the intracellular Ca2+ stores abolished the responses. This shows that the ATP-induced [Ca2+]i increases were in large part, if not entirely, due to the activation of G protein-coupled receptors followed by Ca2+ mobilization from intracellular stores, suggesting an involvement of P2Y receptors. The order of potency of the applied purinergic agonists was UTP > ATP > ATP,S (with all others being only weakly active or inactive). The ATP-induced [Ca2+]i increases could be reduced by the purinergic antagonists PPADS and RB2, but not by suramin. Our findings suggest that extracellular nucleotides in the OE activate SCs via P2Y2/P2Y4 -like receptors and initiate a characteristic intraepithelial Ca2+ wave. © 2008 Wiley-Liss, Inc. [source] Effects of mood stabilizers on the inhibition of adenylate cyclase via dopamine D2 -like receptorsBIPOLAR DISORDERS, Issue 3 2007Liliana P Montezinho Objective:, The mood stabilizing drugs lithium, carbamazepine and valproate modulate brain adenosine monophosphate (cAMP) levels, which are assumed to be elevated in bipolar disorder patients. The aim of this work was to investigate how these three mood stabilizing agents affect the regulation of cAMP levels by dopamine D2 -like receptors in vitro in rat cortical neurons in culture and in vivo in the rat prefrontal cortex. Methods:, The production of cAMP was measured in the cultured cortical neurons or in microdialysis samples collected from the prefrontal cortex of freely moving rats using the [8- 3H] and [125I] radioimmunoassay kits. Results:,In vitro and in vivo data showed that the treatment with the mood stabilizing drugs had no effect on basal cAMP levels in vitro, but had differential effects in vivo. Direct stimulation of adenylate cyclase (AC) with forskolin increased cAMP levels both in vitro and in vivo, and this effect was significantly inhibited by all three mood stabilizers. Activation of dopamine D2 -like receptors with quinpirole partially inhibited forskolin-induced increase in cAMP in untreated cultures, but no effect was observed in cortical neuron cultures treated with the mood stabilizing drugs. Similar results were obtained by chronic treatment with lithium and valproate in the prefrontal cortex in vivo. However, surprisingly, in carbamazepine-treated rats the activation of dopamine D2 -like receptors enhanced the responsiveness of AC to subsequent activation by forskolin, possibly as a consequence of chronic inhibition of the activity of the enzyme. Conclusions:, It was shown that each of these drugs affects basal- and forskolin-evoked cAMP levels in a distinct way, resulting in differential responses to dopamine D2 -like receptors activation. [source] Cannabinoids inhibit noradrenergic and purinergic sympathetic cotransmission in the rat isolated mesenteric arterial bedBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2007P Pakdeechote Background and purpose: Noradrenaline and ATP are sympathetic co-transmitters. In the rat perfused mesenteric bed cannabinoids have been shown to modify the overall response to sympathetic nerve stimulation. This study has assessed whether cannabinoid receptor activation modulates differentially the noradrenergic and purinergic components of sympathetic vasoconstriction. Experimental approach: Rat mesenteric beds were perfused with physiological salt solution and the effects of cannabinoids on responses to nerve stimulation, or exogenous noradrenaline or ,,, -methylene ATP (,,, -meATP; P2X receptor agonist) were determined after raising tone with U46619. The effects of cannabinoids on the noradrenaline and ATP components of sympathetic neurotransmission were assessed using the ,1 -adrenoceptor antagonist, prazosin, or after P2X receptor desensitization with ,,, -meATP. Key results: Anandamide, WIN 55,212-2 and CP55,940 attenuated sympathetic neurogenic vasoconstrictor responses. The inhibitory actions of anandamide and WIN 55,212-2 were blocked by LY320135, a CB1 receptor antagonist, but not by SR144528, a CB2 receptor antagonist. The inhibitory actions of CP55,940 were unaffected by LY320135 and SR144528. WIN 55,212-3, the inactive S(,) enantiomer of WIN 55,212-2, had no effect on sympathetic neurogenic responses. None of the cannabinoids affected contractile responses to exogenous noradrenaline or ,,, -meATP. Anandamide and WIN 55,212-2 inhibited both the noradrenaline and ATP components of the sympathetic neurogenic contractile responses, with effects on the ATP component being most marked. Conclusions and implications: These results indicate that prejunctional CB1 -like receptors mediate the sympathoinhibitory action of anandamide and WIN 55,212-2, but not CP55,940, in the rat mesenteric bed. Cannabinoids inhibit both the noradrenergic and purinergic components of sympathetic neurotransmission. British Journal of Pharmacology (2007) 152, 725,733; doi:10.1038/sj.bjp.0707397; published online 16 July 2007 [source] Collar-induced elevation of mRNA and functional activity of 5-HT1B receptor in the rabbit carotid arteryBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2000Inge S Geerts Hypersensitivity to serotonin (5-HT) develops in rabbit collared carotid arteries. Previous data demonstrated the involvement of 5-HT1 -like receptors which are not active in normal carotid arteries. This study investigated the interaction in the rabbit carotid artery between 5-HT and a moderate tone as this can uncover functional 5-HT1 -like receptors. Furthermore, the expression of messenger RNA (mRNA) and protein of 5-HT1B, 5-HT1D and 5-HT2A receptors was addressed. Silicone collars were placed around the carotid arteries of male New Zealand White rabbits for 1 week. Rings from inside (=collar) and outside (=sham) the collar were either mounted in isolated organ baths for isometric force measurements or frozen in liquid nitrogen to isolate total RNA or proteins which were subsequently analysed by respectively reverse transcriptase-polymerase chain reaction and Western blot analysis. In sham and collared rings concentration-response curves (CRC's) to 5-HT were monophasic. Only in collared segments the presence of a 5-HT2A antagonist (spiperone or ketanserin, 0.1 ,M) revealed a biphasic CRC which was even more pronounced when a moderate tone was induced by KCl pointing to functional 5-HT1 -like receptors. The rabbit carotid artery constitutively expressed 5-HT1B and 5-HT2A mRNA, not 5-HT1D mRNA. Manipulation of the carotid artery increased the 5-HT1B mRNA level. Collar placement raised it even further. The 5-HT2A mRNA level remained unchanged. All the anti-5-HT receptor antibodies tested resulted in variable, non specific patterns with multiple bands. In conclusion, collar placement elevates mRNA expression and activity of the 5-HT1B receptor in the rabbit carotid artery. British Journal of Pharmacology (2000) 131, 1723,1731; doi:10.1038/sj.bjp.0703732 [source] Listeria monocytogenes infection in the face of innate immunityCELLULAR MICROBIOLOGY, Issue 5 2009Sinead C. Corr Summary Pathogen recognition and induction of immune responses are important for efficient elimination of infection. However, pathogens such as Listeria monocytogenes employ strategies to evade or modulate these defences, thus creating a more favourable environment that ensures their survival and pathogenesis. New insights into these strategies, particularly those targeting innate immunity, have recently emerged. L. monocytogenes is initially detected at the cell surface or in phagosomes by toll-like receptor 2 and in the cytosol by nuclear oligodimerization domain (NOD)-like receptors (NOD1, NOD2) and NALP3 and Ipaf. It carries out N-deacetylation of peptidoglycan to avoid this detection by toll-like receptor 2 and NOD-like receptors. L. monocytogenes modulates transcription of host immunity genes through modification of histones and chromatin remodelling. Furthermore, L. monocytogenes has recently been shown to avoid autophagy and induce apoptosis in immune effector cells. In this review we discuss some of these strategies, which have provided new insights into the interaction between L. monocytogenes and the immune response at a crucial stage of infection. [source] Activating and inhibitory killer immunoglobulin-like receptors (KIR) in haploidentical haemopoietic stem cell transplantation to cure high-risk leukaemiasCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009A. Moretta Summary A number of experimental studies have shown that natural killer (NK) cells can eliminate cancer cells and the mechanisms involved in this effect have been uncovered during the last two decades. Clinical data from haploidentical haematopoietic stem cell transplantation (haplo-HSCT) revealed that NK cells were responsible for remarkably favourable effects in both adult and paediatric high-risk leukaemias. NK receptors specific for major histocompatibility complex (MHC) class I molecules, including killer immunoglobulin (Ig)-like receptors (KIR) and CD94/NKG2A, play a major role in the anti-leukaemia effect (mediating either inhibitory or activating signals). Haplo- HSCT requires a heavy conditioning regimen for the patient and the use of large numbers of T cell-depleted HSC to be grafted. After transplantation, natural killer cells develop from HSC shortly after engraftment and may include ,alloreactive' NK cells that kill leukaemic cells and prevent graft- versus -host disease (GvHD). Alloreactive NK cells are characterized by the expression of KIR that are not engaged by any of the human leucocyte antigen (HLA) class I alleles expressed by the patient. Their generation is dependent upon the existence of a KIR/HLA class I mismatch between donor and recipient. Novel important information on the function and specificity of different KIR has been obtained recently by the analysis of donor-derived alloreactive NK cells in a cohort of paediatric patients given haplo-HSCT to cure acute, high-risk leukaemias. [source] | |||||||||||||