The role of adenosine receptors in the action of theophylline on human peripheral blood mononuclear cells from healthy and asthmatic subjects.
1. The aim of the present study was to investigate the role of adenosine A2b receptors in the anti-proliferative action of theophylline in human peripheral blood mononuclear cells (HPBMC) from healthy and asthmatic subjects. 2. Theophylline significantly inhibited PHA-induced proliferation of HPBMC from both healthy and asthmatic donors but only at relatively high concentrations at 1 mM (P<0.05). Enprophylline, a drug which also acts as a non-selective phosphodiesterase (PDE) inhibitor and is a selective A2b receptor antagonist, had no significant effect on proliferation of cells from either group at concentrations up to 10 microM (P>0.05; n=6). 3. Adenosine deaminase (2 u ml(-1)), which metabolizes adenosine, had no significant effect on PHA-induced HPBMC proliferation over a range of concentrations (0 - 8 microg ml(-1)) in cells from either healthy or asthmatic subjects. 4. The adenosine receptor agonists N(6)-cyclopentyladenosine (CPA, A1-selective) and 5'-N-ethylcarboxamidoadenosine (NECA, A1/A2) produced a small but significant inhibition of PHA-induced proliferation of HPBMC from healthy and asthmatic subjects (10 microM, P<0.05; n=6). In contrast, 5'-N-ethylcarboxamido-2-[4-(2-]carboxyethyl)phenethyl]adenosine (CGS21680, A2a-selective) was without significant effect (P>0.05; n=6). 5. The adenosine receptor antagonist alloxazine (A2b-selective) had no significant effect, while 8(3-chlorostyryl)caffeine,(CSC, A2a-selective) significantly inhibited PHA-induced proliferation of HPBMC from both groups (P<0.05; n=6). 6. Our results suggest that endogenous or exogenous adenosine has little effect on the proliferation of HPBMC obtained from healthy or asthmatic subjects. Thus it would appear that the effect of high concentrations of theophylline is not related to adenosine receptor antagonism.
Landells
L J
LJ
Sackler Institute of Pulmonary Pharmacology, Division of Pharmacology and Therapeutics, GKT School of Biomedical Sciences, King's College London, Guy's Campus, London Bridge, London SE1 9RT, UK.
Jensen
M W
MW
Orr
L M
LM
Spina
D
D
O'Connor
B J
BJ
Page
C P
CP
D000243:Adenosine Deaminase / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043704:Receptor, Adenosine A2B; D013806:Theophylline / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D010835:Phytohemagglutinins; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043704:Receptor, Adenosine A2B; D013806:Theophylline; D000243:Adenosine Deaminase