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 antiproliferative action of theophylline in hut-nan perip heral blood mononuclear cells (HPBMC) from healthy and asthmatic subjects. 2 Theophylline significantly inhibited PHA-induced proliferation of HPBMC f rom both healthy and asthmatic donors but only at relatively high concentra tions at 1 mM (P<0.05). Enprophylline, a drug which also acts as a non-sele ctive phosphodiesterase (PDE) inhibitor and is a selective A2b receptor ant agonist, had no significant effect on proliferation of cells from either gr oup at concentrations up to 10 mu M (P>0.05; n=6). 3 Adenosine deaminase (2 u ml(-1)). which metabolizes adenosine, had no sig nificant effect on PHA-induced HPBMC proliferation over a range of concentr ations (0-8 mu g ml(-1)) in cells from either healthy or asthmatic subjects . 4 The adenosine receptor agonists N-6-cyclopentyladenosine (CPA, Al-selecti ve) and 5'-N-ethylcarboxamidoadenosine (NECA, A1/A2) produced a small but s ignificant inhibition of PHA-induced proliferation of HPBMC from healthy an d asthmatic subjects (10 mu M, P<0.05; n=6). In contrast, 5'-N-ethylcarboxa mido-2-[4-(2-]carboxyethyl)phenethyl]adenosine (CGS21680, A2a-selective) wa s without significant effect (P>0.05, n=6). 5 The adenosine receptor antagonist alloxazine (A2b-selective) had no signi ficant effect, while 8(3-chlorostyryl)caffeine,(CSC, A2a-selective) signifi cantly inhibited PHA-induced proliferation of HPBMC from both groups (P<0.0 5: n=6). 6 Our results suggest that endogenous or exogenous adenosine has little eff ect on the proliferation of HPBMC obtained from healthy or asthmatic subjec ts. Thus it would appear that the effect of high concentrations of theophyl line is not related to adenosine receptor antagonism.