Inhibition of neutrophil chemotaxis by purinoceptor agonists.
Adenine nucleotides inhibited fMet-Leu-Phe-activated chemotaxis by rabbit neutrophils in the micromolar concentration range. The sequence of inhibitory effectiveness was ATP[S] greater than ATP greater than ADP greater than AMP greater than adenosine. In the presence of EDTA, inhibition of chemotaxis by ATP occurred to the same degree as in the presence of Ca2+ (and Mg2+), indicating that neither ectonucleotidases nor Ca2+ fluxes across the plasma membrane are of importance for the inhibitory effect. The inhibitory effect of ATP persisted when the nucleotide was removed after preincubation, before the cells were submitted to chemotaxis. Exposure of neutrophils to ApCpp results in desensitization towards inhibition by ATP. Other nucleoside triphosphates, such as XTP, GTP, ITP, CTP and UTP, also inhibited neutrophil migration. The relative potency of the nucleotides, which are used to discriminate between the subtypes of the P2 purinoceptor, was (at a concentration of 50 microM) ATP greater than ApCpp greater than AppNp greater than MeSATP greater than AppCp. The results suggest that inhibition of neutrophil chemotaxis by purinoceptor agonists is mediated by P2 purinoceptors and that the subtype is different from the P2x or P2y purinoceptor.
Elferink
J G
JG
Departments of Medical Biochemistry, Biology, University of Leiden, The Netherlands.
de Koster
B M
BM
Boonen
G J
GJ
de Priester
W
W
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D002364:Caseins / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects*
D000227:Adenine Nucleotides; D002364:Caseins; D002413:Cations, Divalent; D011983:Receptors, Purinergic; D009240:N-Formylmethionine Leucyl-Phenylalanine