%0 Journal Article %1 Lohse1988b %A Lohse, M. J. %A Klotz, K. N. %A Salzer, M. J. %A Schwabe, U. %D 1988 %J Proc Natl Acad Sci U S A %K & A/pharmacology Adenosine-5'-(N-ethylcarboxamide) Adenosine/*analogs Animals Benzofurans Calcimycin/pharmacology Calcium/*physiology Cells/drug Concanavalin Fura-2 Histamine Inositol Kinetics Male Mast Phosphates/metabolism Rats Reference Release/*drug Strains Values derivatives/pharmacology/*physiology effects effects/*physiology Mice %N 23 %P 8875-9 %T Adenosine regulates the Ca2+ sensitivity of mast cell mediator release %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2461558 %V 85 %X Mast cells release histamine and other mediators of allergy in response to stimulation of their IgE receptors. This release is generally thought to be mediated by an elevation of cytosolic Ca2+. Recent evidence suggests that there might be factors that modulate the coupling between Ca2+ levels and mediator release. The present report identifies adenosine as one such modulator. Adenosine and several of its metabolically stable analogues were shown to enhance histamine release from rat peritoneal mast cells in response to stimuli such as concanavalin A. Metabolizing endogenous adenosine with adenosine deaminase dampened the response to stimuli, whereas trapping endogenous adenosine inside mast cells with nucleoside-transport inhibitors markedly enhanced stimulated histamine release. The metabolically stable adenosine analogue 5'-(N-ethylcarboxamido)adenosine (NECA) did not affect the initial steps in the sequence from IgE-receptor activation to mediator release, which are generation of inositol trisphosphate and increase of cytosolic Ca2+. However, NECA did enhance the release induced in ATP-permeabilized cells by exogenous Ca2+, but it had no effect on the release induced by phorbol esters. These data suggest that adenosine sensitizes mediator release by a mechanism regulating stimulus-secretion coupling at a step distal to receptor activation and second-messenger generation.

@article{Lohse1988b, abstract = {Mast cells release histamine and other mediators of allergy in response to stimulation of their IgE receptors. This release is generally thought to be mediated by an elevation of cytosolic Ca2+. Recent evidence suggests that there might be factors that modulate the coupling between Ca2+ levels and mediator release. The present report identifies adenosine as one such modulator. Adenosine and several of its metabolically stable analogues were shown to enhance histamine release from rat peritoneal mast cells in response to stimuli such as concanavalin A. Metabolizing endogenous adenosine with adenosine deaminase dampened the response to stimuli, whereas trapping endogenous adenosine inside mast cells with nucleoside-transport inhibitors markedly enhanced stimulated histamine release. The metabolically stable adenosine analogue 5'-(N-ethylcarboxamido)adenosine (NECA) did not affect the initial steps in the sequence from IgE-receptor activation to mediator release, which are generation of inositol trisphosphate and increase of cytosolic Ca2+. However, NECA did enhance the release induced in ATP-permeabilized cells by exogenous Ca2+, but it had no effect on the release induced by phorbol esters. These data suggest that adenosine sensitizes mediator release by a mechanism regulating stimulus-secretion coupling at a step distal to receptor activation and second-messenger generation.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Lohse, M. J. and Klotz, K. N. and Salzer, M. J. and Schwabe, U.}, biburl = {https://www.bibsonomy.org/bibtex/233191e84b1ef1426178d1b530619e2b0/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {b86e3fe1402bcc5a998306876095abd2}, intrahash = {33191e84b1ef1426178d1b530619e2b0}, issn = {0027-8424 (Print) 0027-8424 (Linking)}, journal = {Proc Natl Acad Sci U S A}, keywords = {& A/pharmacology Adenosine-5'-(N-ethylcarboxamide) Adenosine/*analogs Animals Benzofurans Calcimycin/pharmacology Calcium/*physiology Cells/drug Concanavalin Fura-2 Histamine Inositol Kinetics Male Mast Phosphates/metabolism Rats Reference Release/*drug Strains Values derivatives/pharmacology/*physiology effects effects/*physiology Mice}, month = Dec, note = {Lohse, M J Klotz, K N Salzer, M J Schwabe, U In Vitro United states Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 1988 Dec;85(23):8875-9.}, number = 23, pages = {8875-9}, shorttitle = {Adenosine regulates the Ca2+ sensitivity of mast cell mediator release}, timestamp = {2010-12-14T18:22:56.000+0100}, title = {Adenosine regulates the Ca2+ sensitivity of mast cell mediator release}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2461558}, volume = 85, year = 1988 }