Adenosine system and cell calcium translocation: Interference of calcium channel blockers

Adenosine is able to inhibit in vitro neutrophil functions induced by formyl-methionyl-leucyl-phenylalanine (FMLP) and A23187, but not phorbol 12-myristate 13-acetate (PMA). The inhibiting activity on A23187 is reversed by increasing extracellular Ca++ concentration. The calcium entry blocker flunarizine shows an activity very similar to that of adenosine. Both adenosine and flunarizine prevent Ca++ influx into activated neutrophils as detected by the fluorescent Ca++ chelator Quin-2. Finally, flunarizine binds to the neutrophil membrane and adenosine competitively inhibits flunarizine binding as assessed by 1H-Nuclear Magnetic Resonance (1H-NMR) technique, thus indicating that the two agents share a common binding site on the cell membrane.