Adenosine potentiates mediator release from human lung mast cells.
Micromolar concentrations of adenosine were found to potentiate the release of histamine and leukotriene C4 (LTC4) from immunologically activated human lung mast cells (HLMC). Structurally modified congeners of adenosine including 5'-N-ethylcarboxamideadenosine (NECA) and R-phenylisopropyladenosine (R-PIA) also potentiated mediator release. A rank order of potency was established where NECA greater than R-PIA for the potentiation of both LTC4 production and histamine secretion. Mast cells isolated by either enzymatic or mechanical means from human lung parenchyma were both similarly responsive to the modulatory effects of adenosine and analogues, and the potency series of NECA greater than R-PIA also applied. Moreover, histamine release induced by the calcium ionophore A23187 was augmented by NECA, R-PIA, and adenosine and in that potency order. Dipyridamole, an agent thought to impede the intracellular uptake of adenosine, failed to reverse the nucleoside's enhancement of IgE-mediated secretion. The irreversible inhibitor of adenosine deaminase, deoxycoformycin, did not modify the adenosine enhancement of stimulated secretion. Low concentrations of methylxanthines, which antagonize responses mediated at cell surface adenosine receptors, were inconsistent in their effects. Theophylline modestly reversed the adenosine-induced potentiation of IgE-mediated LTC4 generation but not histamine release. Studies employing 8-phenyltheophylline were complicated by the methylxanthine possessing inhibitory properties of its own at concentrations expected to antagonize a nucleoside-mediated effect. In total, these results suggest that the response of HLMC to adenosine describes properties most consistent with an A2/Ra-like process, although an interaction via an, as yet, uncharacterized cell surface receptor cannot be excluded.
Peachell
P T
PT
Department of Medicine, Johns Hopkins University School of Medicine, Good Samaritan Hospital, Baltimore, Maryland 21239.
Columbo
M
M
Kagey-Sobotka
A
A
Lichtenstein
L M
LM
Marone
G
G
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004357:Drug Synergism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009705:Nucleosides / Q000494:pharmacology; D015649:Pentostatin; D011983:Receptors, Purinergic / Q000502:physiology; D013189:SRS-A / Q000378:metabolism; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
D009705:Nucleosides; D011983:Receptors, Purinergic; D013189:SRS-A; D014970:Xanthines; D003070:Coformycin; D019830:Adenosine-5'-(N-ethylcarboxamide); D015649:Pentostatin; D004176:Dipyridamole; D000243:Adenosine Deaminase; D000241:Adenosine