Diadenosine polyphosphates induce intracellular Ca2+ mobilization in human neutrophils via a pertussis toxin sensitive G-protein.
The diadenosine polyphosphates diadenosine 5',5"'-P1,P3-triphosphate (Ap3A), diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), diadenosine 5',5"'-P1,P5-pentaphosphate (Ap5A) and diadenosine 5',5"'-P1,P6-hexaphosphate (Ap6A) all stimulated increases in intracellular Ca2+ in human neutrophils. Maximal increases in intracellular Ca2+ of 650 nM were obtained at dinucleotide concentrations of 500-700 microM. These increases in intracellular, Ca2+ were completely abolished by pre-treatment of the neutrophils with pertussis toxin and were hardly affected when the extracellular buffer was devoid of Ca2+. On the other hand, adenosine triphosphate (ATP) could stimulate much greater increases in intracellular Ca2+ (up to 1.1 microM) at much lower concentrations (half maximal responses obtained at around 5 microM ATP). Receptor de-sensitization experiments indicate that human neutrophils may possess two types of P2-purinoceptors. The first of these may bind ATP (but not the dinucleotides) with high affinity whilst the second may bind the dinucleotides with lower affinity and also bind ATP.
Gasmi
L
L
Department of Biochemistry, University of Liverpool, UK.
McLennan
A G
AG
Edwards
S W
SW
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D018929:Cell Culture Techniques; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015226:Dinucleoside Phosphates; D018048:Receptors, Purinergic P2; D010566:Virulence Factors, Bordetella; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium