Abstract

Adenosine was found to modulate the activity of the human basophil and lung mast cell (HLMC) differently. In the basophil, adenosine inhibited the anti-IgE stimulated release of histamine and leukotriene C4 (LTC4) and increased total cell cyclic AMP (cAMP) levels. Substituted adenosine analogs had a rank order potency of: N-ethylcarboxamideadenosine (NECA) greater than 2-chloroadenosine greater than R-phenylisopropyladenosine for the inhibition of immunoglobulin E-triggered mediator release from the basophil and increases in cAMP levels. The adenosine receptor antagonist, 8-phenyltheophylline, antagonized both the NECA-induced inhibition of mediator release and elevations in cyclic nucleotide. The purinergic transport inhibitor, dipyridamole, reversed the inhibition by adenosine of histamine release but not LTC4 generation, suggesting that these two actions are mechanistically separable. Dipyridamole failed to modify the adenosine-induced elevation in cAMP. In contrast to the findings in the basophil, the response to adenosine in the HLMC was biphasic in nature. Thus, at low concentrations of the nucleoside, adenosine potentiated the release of histamine and LTC4 from immunologically activated HLMC, whereas at higher concentrations a counteractive inhibitory process was observed. Analogs of adenosine had the same effects on HLMC; NECA was more potent than R-phenylisopropyladenosine for both the potentiating and inhibitory components of the biphasic response. Low concentrations of adenosine analogs, which potentiated secretion, initiated modest elevations in cAMP levels, whereas higher concentrations, which inhibited secretion, significantly augmented cAMP levels. Although R-phenylisopropyladenosine was almost as potent as NECA at elevating cAMP in HLMC, it was not as efficacious. The NECA-induced modulation of HLMC mediator release and elevations in cAMP were antagonized by 8-phenyltheophylline.(ABSTRACT TRUNCATED AT 250 WORDS)