CALCIUM RESPONSES ELICITED BY NUCLEOTIDES IN MACROPHAGES - INTERACTION BETWEEN 2 RECEPTOR SUBTYPES

The responses elicited by ATP and UTP in macrophages (measured by micr ofluorescence and in patch-clamp) present marked differences. The rele ase of Ca2+ from intracellular stores induced by ATP is due to the act ivation of P2U receptors. These receptors can be activated by ATP4- an d by MgATP2-, with apparent K0.5 values of 0.65 and 6.5 muM, respectiv ely. 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 open ing of P2Z receptor channels triggered by adenosine-5'-O(1-thiotriphos phate) or ATP but not by UTP. The form of ATP that activates P2Z recep tors is ATP4- (with a K0.5 of 0.5 muM). In voltage-clamped cells, the inward current activated by ATP4- is transient, partly because it inac tivates and partly because it is rapidly masked by the development of a quinine-sensitive Ca2+-dependent K+ current. In current-clamp, macro phages stimulated by UTP remain normally polarized, whereas ATP depola rizes them. This P2Z-mediated depolarization results in an inhibition of the influx of Ca2+, which explains part of the difference between t he time courses of the Ca2+ responses elicited by ATP and UTP.