ACTIVATION BY CHEMOTACTIC PEPTIDE OF A RECEPTOR-OPERATED CA2-60 CELLS( ENTRY PATHWAY IN DIFFERENTIATED HL)

N-Formyl-methionyl-leucyl-phenylalanine (fMLP) is able to accelerate C a2+ entry into differentiated HL60 cells by a rather indirect mechanis m consisting of the opening of a plasma membrane pathway activated by the emptying of the intracellular Ca2+ stores caused by the agonist. T his Ca2+ pathway can also be fully activated by Ca2+ pathway store dep letion with thapsigargin. We show here that, in addition to this store -operated Ca2+ entry pathway (SOCP), fMLP is able to activate another receptor-operated Ca2+ pathway in thapsigargin-treated HL60 cells diff erentiated for 24 h with dimethyl sulfoxide. Activation by fMLP was pr oduced even in cells with fully empty Ca2+ stores. It started 30 s aft er fMLP addition, was maximal after 2 min and then disappeared within 5 min. This pathway was similar to SOCP in that it allowed passage of Mn2+ and Ba2+ and was antagonized by Ni2+ and by cytochrome P-450 inhi bitors. fMLP is also able to inhibit SOCP by a mexhanism involving pro tein phosphorylation. Both the fMLP-induced activation of Ca2+ entry a nd the inhibition of SOCP were prevented by pretreatment with pertussi s toxin. However, the first appeared earlier than the last along diffe rentiation of HL60 cells. This suggests that the inhibition of SOCP re quires not only the development of fMLP receptors but also an addition al component placed distally to the G protein in the transduction mech anism.