Abstract
The antigen induced stimulation of mast cells by aggregation of Fc epsilon RI receptors activates a signal transduction cascade leading to release of mediators of inflammation like histamine, arachidonic acid metabolites and cytokines. In this study we investigated a series of structurally related anti-allergic drugs, containing a common lipophilic diphenylmethyl piperazinyl tail and head groups that differ in lipophilicity. Effects of these drugs on various steps of the signal transduction cascade was investigated to gain insight into the mechanism of action of these drugs. It appeared that addition of the drugs to resting cells induced changes in the tyrosine phosphorylation of cellular proteins. The most active anti-allergics in inhibiting exocytosis, AL3264 and oxatomide, also induced the largest changes in phosphorylation. The effects of the drugs on tyrosine phosphorylation after cell activation was complex. Additionally, Ca2+ fluxes were investigated. Ca2+ efflux from the cells was negligibly influenced by the active drugs. However, the drugs inhibited influx from extracellular Ca2+, which was correlated with the effects of the drugs on inhibition of exocytosis and on membrane stabilization induced by the drugs, measured...Continue Reading
References
Jun 1, 1992·Trends in Pharmacological Sciences·W A Catterall, J Striessnig
Sep 25, 1992·Biochemical Pharmacology·N YamadaK Umezu
Oct 1, 1992·The Journal of Allergy and Clinical Immunology·F E Simons
Mar 1, 1990·Agents and Actions·H Y Lau, F L Pearce
Oct 1, 1987·Cell Calcium·G GiglK Gietzen
Feb 1, 1988·European Journal of Biochemistry·S Ran, B Rivnay
Apr 1, 1989·Agents and Actions·O ThastrupM R Hanley
Dec 1, 1987·The Biochemical Journal·P H Cobbold, T J Rink
Mar 10, 1994·Biochimica Et Biophysica Acta·R TeshimaT Terao
Mar 2, 1994·Biochemical Pharmacology·B BerthonA Weyer
Mar 1, 1995·Molecular and Cellular Biology·V M Rivera, J S Brugge
Feb 1, 1995·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·M J FischerL H Janssen
Dec 1, 1994·Agents and Actions·O ThastrupM R Hanley
Feb 15, 1995·The Journal of Physiology·L Zhang, M A McCloskey
Dec 1, 1994·The Journal of Allergy and Clinical Immunology·A M Scharenberg, J P Kinet
Nov 29, 1994·Biochemical Pharmacology·C C FelderC Mathes
Oct 1, 1994·Pflügers Archiv : European journal of physiology·D FranziusR Penner
Mar 1, 1994·Trends in Pharmacological Sciences·C FasolatoT Pozzan
Feb 1, 1993·Trends in Biochemical Sciences·F S MennitiS B Shears
May 1, 1993·Cell Calcium·R D Berlin, S F Preston
May 1, 1993·Immunology Today·M A Beaven, H Metzger
Citations
Dec 3, 1999·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·J P Rihoux
May 16, 2014·PloS One·Masahiro MyojoYasunobu Hirata
Aug 2, 2005·Developmental and Comparative Immunology·Erjun Ling, Xiao-Qiang Yu
Jan 25, 2006·Personality and Social Psychology Review : an Official Journal of the Society for Personality and Social Psychology, Inc·Bert H Hodges, Anne L Geyer
Jul 29, 2006·Journal of Lesbian Studies·Melanie D OtisSharon S Rostosky
Jan 30, 2007·Scandinavian Journal of Psychology·David De Cremer
Nov 5, 2008·Veterinary Dermatology·Monika M WelleSilvia Rüfenacht
May 3, 2019·Personality & Social Psychology Bulletin·Kenneth TanBenjamin W Hadden
Aug 27, 1998·Biochemical Pharmacology·M J FischerL H Janssen