Abstract
Stimulated mast cells produce and release adenosine, and the release of mast cell mediators is potentiated by adenosine, yet very little is known regarding mast cell purine metabolism. Because AICAR has been shown to alter metabolism of adenosine and accelerate the repletion of ATP pools in other tissues, its effect on mast cell function was examined. Simultaneous addition of AICAR (25-250μM) with A23187 or specific antigen did not alter mouse bone marrow-derived mast cell (MMC) β-hexosaminidase (β-hex) release in the absence or presence of exogenous adenosine, nor did a 60-min preincubation with AICAR. However, MMCs cultured for 6 days in the presence of 10-100μM AICAR demonstrate a slightly increased spontaneous release of β-hex and histamine, and a markedly decreased mediator release response to A23187 or antigen equal to 45.2±0.1% of release from control cells (p<.005) with or without the additional presence of adenosine (10−4-10−10M). Exposure to these concentrations of AICAR had no effect on MMC viability, rate of division, or basal β-hex concentrations. An unusual ribonucleotide triphosphate previously identified as a regulatory molecule in formyl-depleted cells, AICAR triphosphate (ZTP), has been identified in 6-day cultures of AICAR-treated MMCs at a concentration of 0.065±0.002nmoles/106 cells (controls < 0.005nmoles ZTP/106 cells). A modest enhancement (∼15%) of intracellular ATP levels is also seen in the AICAR MMCs. This global inhibition of MMC mediator release may prove to be important in the treatment of allergic diseases.
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Marquardt, D., Gruber, H. INHIBITION OF HAST CELL MEDIATOR RELEASE BY 5-AMINO-4-IMIDAZOLECARB0XAMIDE RIBOSIDE (AICAR): 124. Pediatr Res 19, 764 (1985). https://doi.org/10.1203/00006450-198507000-00144
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DOI: https://doi.org/10.1203/00006450-198507000-00144