Evidence that IgE receptor stimulation increases adenosine release from rat basophilic leukaemia (RBL-2H3) cells.
Adenosine may play a role in asthma by enhancing inflammatory mediator release from lung mast cells. In this study, we investigated whether adenosine is released from cultured rat basophilic leukaemia (RBL-2H3) cells in response to antigen challenge and whether released adenosine enhances mediator release. RBL-2H3 cells closely resemble mucosal mast cells, the most common type of mast cell in lung tissue, and they express adenosine A3 receptors (which have been associated with asthma). Measurement of adenosine in RBL-2H3 cell incubation medium was possible if adenosine metabolism was inhibited by EHNA (10 microM; an adenosine deaminase inhibitor) and 5-iodotubericidin (5-IT; 10 microM; an adenosine kinase inhibitor). Basal adenosine concentration increased up to 1.0 microM during a 90 min incubation; after antigen challenge, adenosine concentration was increased by 0.3-0.4 microM above basal. Antigen-induced adenosine release ranged from 30-70 nmol/1.25x10(6) cells. Antigen-induced mediator release (beta-hexosaminidase and [3H]5-hydroxytryptamine) was increased by APNEA, an adenosine A3 receptor agonist (EC50 approximately 20 nm) but inhibited by EHNA and 5-IT, despite increased adenosine levels. This inhibition was not blocked by the adenosine A1/A2 receptor antagonist DPSPX (5 microM). Therefore, it is unlikely to be related to adenosine receptor activation. In conclusion, although our data provide no direct support for a positive feedback effect of adenosine on mast cell mediator release, the observation that IgE receptor stimulation increases adenosine production in cells which express stimulatory A3 receptors is consistent with this hypothesis.
Lloyd
H G
HG
Department of Pharmacology, The University of Sydney, Sydney, NSW, 2006, Australia. hgelloyd@pharmacol.su.oz.au
Ross
L
L
Li
K M
KM
Ludowyke
R I
RI
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003594:Cytoplasmic Granules / Q000378:metabolism; D015471:Leukemia, Basophilic, Acute; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D043684:Receptor, Adenosine A3; D017455:Receptors, IgE / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
C086112:N(6)-2-(4-aminophenyl)ethyladenosine; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D017455:Receptors, IgE; C034214:5-iodotubercidin; D012701:Serotonin; C010192:9-(2-hydroxy-3-nonyl)adenine; D001619:beta-N-Acetylhexosaminidases; D000225:Adenine; D000241:Adenosine; D014372:Tubercidin