Adenosine inhibits divalent cation influx across human neutrophil plasma membrane via surface adenosine A2 receptors.
Adenosine and its analogues inhibited increases in divalent cation influx stimulated by platelet-activating factor (PAF) and formyl-methionyl-leucyl-phenylalanine (FMLP) in a dose-dependent fashion. This effect was antagonized by theophylline, an adenosine receptor antagonist. When extracellular adenosine was removed by adenosine deaminase, the effect of adenosine was completely abolished. Two adenosine analogues with different affinities for adenosine receptor subtypes, 5'-N-ethylcarboxamideadenosine (NECA) and L-N6-phenylisopropyladenosine (PIA), also inhibited divalent cation influx, NECA being more potent than PIA. These results suggest that adenosine and its analogues inhibit divalent cation influx across neutrophil plasma membranes via surface adenosine A2 receptors. Adenosine had little effect on the initial peaks of intracellular free calcium rises induced by chemoattractants, but it inhibited the subsequent rise in free calcium. Since calcium influx through the divalent cation channels or neutrophil plasma membranes is responsible for maintaining free calcium concentration following the initial peaks, we suggest that adenosine modulates neutrophil function by interfering with this calcium influx.
Tsuruta
S
S
Department of Paediatrics, Kyoto University Hospital, Japan.
Ito
S
S
Mikawa
H
H
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000328:Adult; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology
D002413:Cations, Divalent; D010972:Platelet Activating Factor; D011983:Receptors, Purinergic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013806:Theophylline; D000243:Adenosine Deaminase; D000241:Adenosine; D002118:Calcium