ADENOSINE INHIBITS AND POTENTIATES IGE-DEPENDENT HISTAMINE-RELEASE FROM HUMAN-LUNG MAST-CELLS BY AN A2-PURINOCEPTOR MEDIATED MECHANISM
ADENOSINE INHIBITS AND POTENTIATES IGE-DEPENDENT HISTAMINE-RELEASE FROM HUMAN-LUNG MAST-CELLS BY AN A2-PURINOCEPTOR MEDIATED MECHANISM
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DOI：
10.1016/0006-2952(84)90050-9
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发表时间：
1984-01-01
影响因子：
5.8
通讯作者：
CHURCH, MK
中科院分区：
文献类型：
--
作者：
HUGHES, PJ;HOLGATE, ST;CHURCH, MK
Adenosine, at physiological concentrations, may modulate histamine release from mechanically dispersed human lung mast cells. Addition of adenosine to the dispersed mast cells at times up to 5 min before immunolgical challenge with anti-human IgE inhibited histamine release. When added after this time adenosine caused a small potentiation of immunological histamine release, maximum potentiation occurring with addition of adenosine 5 min after challenge coincidental with the end of the rapid phase of histamine release. Both inhibition and potentiation of histamine release were more pronounced with low levels of immunological challenge. Theophylline, 8-phenyltheophylline, dipyridamole and analogs of adenosine were used to determine the site of action of adenosine on mast cell mediator release. Theophylline and 8-phenyltheophylline displaced the concentration-response lines for both inhibition and potentiation of mediator release by adenosine to the right while dipyridamole, 1 .mu.M, was without significant effect. This suggests that both effects result from interaction of adenosine with cell surface receptors. This was confirmed by demonstrating that the P-site agonist 2'', 5''-dideoxyadenosine produced only inhibition of histamine release, an effect which was inhibited by dipyridamole but not by theophylline. The rank potency order of adenosine analogs, NECA [s''-N-ethylcarboxamide adenosine] > adenosine .gtoreq. L-PIA [L-N6-phenylisopropyladenosine] .gtoreq. D-PIA in both inhibiting and potentiating immunological histamine release suggests that both effects are mediated through activation of cell surface A2-purinoceptors. Since adenosine is released into the circulation of asthmatic subjects following bronchial provocation with antigen, causes bronchoconstriction and has the ability to modulate mast cell histamine release, this nucleoside should be considered as an additional inflammatory mediator of allergic reactions.
