The role of adenosine receptors in the action of theophylline on human peripheral blood mononuclear cells from healthy and asthmatic subjects

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Abstract
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. Theophylline significantly inhibited PHA‐induced proliferation of HPBMC from both healthy and asthmatic donors but only at relatively high concentrations at 1 mM (PP>0.05; n=6). 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 μg ml−1) in cells from either healthy or asthmatic subjects. The adenosine receptor agonists N6‐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 μM, P0.05; n=6). 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 (Pn=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. British Journal of Pharmacology (2000) 129, 1140–1144; doi:10.1038/sj.bjp.0703177