Characterization of receptor-mediated and store-regulated Ca2+ influx in human neutrophils.
1. It is not known to what extent the emptying of intracellular Ca2+ stores participates in the mediation of chemoattractant-induced Ca2+ influx in human neutrophils. To study this question, we compared the properties of bivalent-cation influx in response to the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenyl-alanine (f-MLP) and to the microsomal Ca(2+)-ATPase inhibitor thapsigargin. 2. The influx pathway activated by f-MLP and thapsigargin had identical properties of permeation. Mn2+ influx became saturated at around 1 mM extracellular Mn2+, whereas Ca2+ influx did not become saturated up to concentrations of 10 mM. 3. The influx of the two bivalent cations, Mn2+ and Ca2+, was activated to a similar extent and with identical kinetics of activation. 4. The Mn2+ influx activated by f-MLP and thapsigargin was blocked, with identical dose-inhibition curves, by four imidazole analogues. 5. The same relationship between the emptying of Ca2+ stores and bivalent-cation influx was observed for f-MLP and thapsigargin, with a half-maximal activation of the influx at 40% emptying of intracellular stores. 6. In conclusion, neutrophils possess a single type of Ca(2+)-influx pathway that is activated by receptor agonists and by store depletion. Receptor agonists activate this influx pathway to a large extent, if not completely, through the depletion of intracellular Ca2+ stores.
Demaurex
N
N
Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
Monod
A
A
Lew
D P
DP
Krause
K H
KH
D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008345:Manganese / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D007093:Imidazoles; D011956:Receptors, Cell Surface; D013729:Terpenes; D008345:Manganese; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019284:Thapsigargin; D002118:Calcium