Calcium responses elicited by nucleotides in macrophages. Interaction between two receptor subtypes.
The responses elicited by ATP and UTP in macrophages (measured by microfluorescence and in patch-clamp) present marked differences. The release of Ca2+ from intracellular stores induced by ATP is due to the activation of P2U receptors. These receptors can be activated by ATP4- and by MgATP2-, with apparent K0.5 values of 0.65 and 6.5 microM, respectively. The release of Ca2+ due to activation of P2U receptors by either ATP or UTP is followed by the opening of ionic channels leading to an influx of Ca2+. A second pathway for Ca2+ influx results from the opening of P2Z receptor channels triggered by adenosine-5'-O(1-thiotriphosphate) or ATP but not by UTP. The form of ATP that activates P2Z receptors is ATP4- (with a K0.5 of 0.5 microM). In voltage-clamped cells, the inward current activated by ATP4- is transient, partly because it inactivates and partly because it is rapidly masked by the development of a quinine-sensitive Ca(2+)-dependent K+ current. In current-clamp, macrophages stimulated by UTP remain normally polarized, whereas ATP depolarizes them. This P2Z-mediated depolarization results in an inhibition of the influx of Ca2+, which explains part of the difference between the time courses of the Ca2+ responses elicited by ATP and UTP.
Alonso-Torre
S R
SR
Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique URA 295, Ecole Normale Supérieure, Paris, France.
Trautmann
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D011983:Receptors, Purinergic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013873:Thionucleotides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*
D011983:Receptors, Purinergic; D013729:Terpenes; D013873:Thionucleotides; C017817:adenosine 5'-(1-thio)triphosphate; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium; D002118:Calcium; D014544:Uridine Triphosphate