Inhibitory effects of benzodiazepines on the adenosine A(2B) receptor mediated secretion of interleukin-8 in human mast cells.
作者： Kristina Hoffmann , Rosa Altarcheh Xifró , Julia Lisa Hartweg , Petra Spitzlei , Kirsten Meis
DOI: 10.1016/J.EJPHAR.2012.12.003
关键词:
摘要: The activation of adenosine A(2B) receptors in human mast cells causes pro-inflammatory responses such as the secretion interleukin-8. There is evidence for an inhibitory effect benzodiazepines on cell mediated symptoms patients with systemic disease. Therefore, we investigated effects receptor interleukin-8 production leukaemia (HMC1) by enzyme linked immunosorbent assay. analogue N-ethylcarboxamidoadenosine (NECA, 0.3-3 μM) increased about 5-fold above baseline. This was attenuated antagonist MRS1754 (N-(4-cyanophenyl)-2-{4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy}-acetamide) 1 μM. In addition, diazepam, 4'-chlorodiazepam and flunitrazepam (1-30 markedly reduced NECA-induced that order potency, whereas clonazepam showed only a modest inhibition. diazepam not altered flumazenil 10 μM or PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide) Diazepam expression mRNA encoding Moreover, increasing NECA cAMP-response element- nuclear factor activated t-cells-driven luciferase reporter gene activities HMC1 cells. Neither nor affected increases cellular cAMP levels CHO Flp-In stably expressing recombinant receptors, excluding direct action receptors. conclusion, this first study showing rank potency indicates involvement atypical benzodiazepine binding site.
sci-hub.se 参考文章(34)
Gary Heebner, Peter Gwynne, Drug Discovery: 5 Science. ,vol. 298, pp. 1067- 1073 ,(2002)
Arnaud Beurdeley-Thomas, Laurent Miccoli, Stephane Oudard, Bernard Dutrillaux, Marie F. Poupon, The peripheral benzodiazepine receptors: a review. Journal of Neuro-oncology. ,vol. 46, pp. 45- 56 ,(2000) , 10.1023/A:1006456715525
Igor Feoktistov, Italo Biaggioni, Role of adenosine A(2B) receptors in inflammation. Advances in pharmacology (San Diego). ,vol. 61, pp. 115- 144 ,(2011) , 10.1016/B978-0-12-385526-8.00005-9
Jürgen Homann, Ulrich W. Kolck, Andreas Ehnes, Thomas Frieling, Martin Raithel, Gerhard J. Molderings, Die systemische Mastozytose – Standortbestimmung einer internistischen Erkrankung Medizinische Klinik. ,vol. 105, pp. 544- 553 ,(2010) , 10.1007/S00063-010-1093-8
Kristina Hoffmann, Uta Sixel, Francesca Di Pasquale, Ivar von Kügelgen, Involvement of basic amino acid residues in transmembrane regions 6 and 7 in agonist and antagonist recognition of the human platelet P2Y12-receptor Biochemical Pharmacology. ,vol. 76, pp. 1201- 1213 ,(2008) , 10.1016/J.BCP.2008.08.029
Mohamed Bidri, Bernard Royer, Geneviève Averlant, Georges Bismuth, Jean-Jacques Guillosson, Michel Arock, Inhibition of mouse mast cell proliferation and proinflammatory mediator release by benzodiazepines. Immunopharmacology. ,vol. 43, pp. 75- 86 ,(1999) , 10.1016/S0162-3109(99)00046-6
Scott S Downing, Yan T Lee, David H Farb, Terrell T Gibbs, Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABAA receptors supports an allosteric model of modulation British Journal of Pharmacology. ,vol. 145, pp. 894- 906 ,(2005) , 10.1038/SJ.BJP.0706251
Kenneth A. Jacobson, Zhan-Guo Gao, Adenosine receptors as therapeutic targets Nature Reviews Drug Discovery. ,vol. 5, pp. 247- 264 ,(2006) , 10.1038/NRD1983
Peter Mayer, Annette Viktoria Hinze, Anja Harst, Ivar von Kügelgen, A2B receptors mediate the induction of early genes and inhibition of arterial smooth muscle cell proliferation via Epac Cardiovascular Research. ,vol. 90, pp. 148- 156 ,(2011) , 10.1093/CVR/CVQ371
H Friedman, David J Greenblatt, Gary R Peters, Carl M Metzler, Melody D Charlton, Jerold S Harmatz, Edward J Antal, Elmer C Sanborn, Steven F Francom, Pharmacokinetics and pharmacodynamics of oral diazepam: Effect of dose, plasma concentration, and time Clinical Pharmacology and Therapeutics. ,vol. 52, pp. 139- 150 ,(1992) , 10.1038/CLPT.1992.123