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Own Receptor (own + receptor)
Selected AbstractsMorphine-like substance in leech gangliaFEBS JOURNAL, Issue 8 2000Evidence, immune modulation Binding experiments followed by measurement of nitric oxide release revealed an opiate alkaloid high affinity receptor with no affinity to opioids, representing a new µ-subtype receptor in the brain of the leech Theromyzon tessulatum. In addition, evidence of morphine-like substances was found in immunocytochemical studies and HPLC coupled to electrochemical detection (500 mV and 0.02 Hz). Based on previous evidence of the involvement of morphine as an immune response inhibitor, we demonstrate that in leech ganglia injection of lipopolysaccharide (LPS; a potent immunostimulatory agent derived from bacteria) provoked an increase in the level of ganglionic morphine-like substances after a prolonged latency period of 24 h (from 2.4 ± 1.1 pmol per ganglion to 78 ± 12.3 pmol per ganglion; P < 0.005; LPS injected 1 µg·mL,1); this effect is both concentration- and time-dependent. Finally, we have demonstrated that morphine, after binding to its own receptor, inhibits leech immunocyte activation through adenylate cyclase inhibition and nitric oxide release. This report confirms that morphine is an evolutionarily stable potent immunomodulator. [source] Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitisHEPATOLOGY, Issue 1 2002Arndt Vogel Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are immune-mediated chronic inflammatory diseases of the liver of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. 1,25-Dihydroxyvitamin D3 has been implicated as an immunomodulator, which acts through its own receptor (VDR). Polymorphisms of the VDR have been linked to a variety of autoimmune diseases. In this study VDR polymorphisms were analyzed in 123 patients with AIH, 74 patients with PBC, and 214 controls. VDR polymorphisms were assessed by BsmI, TaqI, ApaI, and Fok endonuclease digestion after specific polymerase chain reaction (PCR) amplification. We found a significant association between the BsmI polymorphisms in PBC patients in comparison with controls (,2 = 9.49, P = .009). Furthermore we detected a significant association of the Fok polymorphims in AIH patients in comparison to controls (,2 = 9.71, P = .008) indicating a genetic link of VDR polymorphisms to autoimmune liver diseases such as PBC and AIH in German patients. These findings contribute to the knowledge of the complex events determining immunologic tolerance in the liver. Further studies are needed to elucidate the mechanisms by which the vitamin D receptor contributes to the development of autoimmune diseases. [source] Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblastsCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2008A. Borowski Summary Background IL-13 promotes acute allergic asthma and is discussed to play a role in late asthmatic features such as fibrotic processes and airway remodelling. The contributions of IL-13-mediated mechanisms to subepithelial events related to fibrosis are not yet settled. Objective We investigated the impact of IL-13 on lung epithelial cells as apoptotic effector and on lung fibroblasts as inducer of pro-fibrotic gene expression. Methods Using the two lung epithelial cell lines A549 and BEAS-2B as well as primary lung epithelial cells, we investigated the capability of IL-13 to induce apoptosis by both flow-cytometry and ELISA. The ability of IL-13 to increase the expression of pro-fibrotic genes and to exert influence on the expression of its own receptor was investigated by real-time quantitative PCR measurement of mRNAs encoding collagen I, collagen III, basic fibroblast growth factor (bFGF), ,-smooth muscle actin (,-SMA) and the IL-13 receptor ,1 (IL-13R,1) chain in human primary lung fibroblasts. The specificity of IL-13-mediated cellular responses was confirmed by means of an inhibitory monoclonal antibody directed to the IL-13 receptor. Results IL-13 induces apoptosis in lung epithelial cell lines as well as in primary lung epithelial cells. Furthermore, IL-13 increases the expression of mRNA for ,-SMA and collagen III, but not for bFGF in human primary lung fibroblasts. The susceptibility of lung fibroblasts to IL-13-induced up-regulation of pro-fibrotic genes is associated with the regulation of IL-13 receptor expression. IL-13-dependent fibrosis-associated effects could be inhibited by antibody-mediated blockade of the IL-13R,1 subunit. Conclusion Our findings indicate a function of IL-13 as a mediator in fibrotic processes leading to loss of functional airway tissue in asthma. They also highlight the therapeutic potential of specifically targeting the interaction between IL-13 and its receptor. [source] Effect of insulin on rat ovarian leptin expression by immunohistochemical stainingJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2003Naci Kemal Kuscu Abstract Aim:, Leptin and insulin may interact in regulating ovarian steroid synthesis. The objective of this study was to investigate immunohistochemical staining of leptin in normal rat ovarian tissues and in rats treated with insulin and insulin plus human chorinoic gonadotropin (hCG). Methods:, Paraffin blocks of rat ovarian tissues from a previous study, in which 18 adult, female Wistar rats with an average weight of 250 g were divided into three groups to receive either saline solution, human insulin (2 U/day) or human insulin (2 U/day) plus hCG (4 U/day) for 4 weeks, were used in this study to compare the effects on leptin staining. The results were analysed using a semiquantitative scoring system, such as mild, moderate and strong. Results:, No staining was observed in granulosa cells and theca interna cells of normal ovarian tissues. Theca externa cells had mild staining intensity (+), corpus luteum had moderate (+ +) and stroma had mild (+) staining intensity. Histological structure was impaired in the insulin group, luteinized cells had mild staining, there was no difference in other cell groups. Only theca externa cells of the developing follicles were stained in insulin plus hCG group, luteinized cells again had mild staining. Conclusions: Besides damaging the rat ovarian structure, insulin reduced staining intensity of leptin in luteinized cells. Insulin may stimulate ovarian steroid synthesis not only through its own receptors, but also by acting on the leptin expression of these cells. [source] Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic isletsBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2001Thomas L Clemens The cloning of the so-called ,parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify its therapeutic potential in a number of diseases. British Journal of Pharmacology (2001) 134, 1113,1136; doi:10.1038/sj.bjp.0704378 [source] | ||||||||||