Dual regulation of neutrophil adenylate cyclase by fluoride and its relationship to cellular activation

Abstract

1 Fluoride stimulated (1-10 mM) and inhibited (10-100 mM) adenylate cyclase of neutrophil membranes in a GTP-independent manner. The latter fluoride concentration range corresponded to that shown previously to induce cellular responses. 2 Dual regulation of cyclase activity was also exhibited by a nonhydrolysable GTP analogue, guanosine 5'[gamma-thio]triphosphate (GTP gamma S). Inhibition was observed at 0.1-10 nM GTP gamma S while stimulation occurred at greater than 10 nM GTP gamma S. 3 Relatively high levels (greater than microM) of formylmethionyl-leucyl-phenylalanine inhibited adenylate cyclase in the presence of GTP (10 microM). 4 Pertussis toxin pretreatment abolished adenylate cyclase inhibition mediated by GTP gamma S and formylmethionyl-leucyl-phenylalanine but did not influence fluoride-induced inhibition.