Activation and priming of the human neutrophil oxidase response by substance P: distinct signal transduction pathways.
The undecapeptide substance P (SP), both activates and 'primes' the neutrophil NADPH-oxidase response. In this paper we investigate the roles of Ca2+ and actin polymerisation in both the activation and 'priming' of the neutrophil oxidase response by the non-oxidisable SP-analog norleucine-SP (n-SP). We demonstrate that by binding to receptors which were distinct from the formylated peptide receptor, n-SP (100 nM-400 microM) directly triggered the NADPH-oxidase response, elevated cytosolic free Ca2+, and caused the polymerisation of G-actin. However at lower concentrations (1-100 nM), in the absence of these phenomena, n-SP primed the oxidase response to the peptide f-Met-Leu-Phe. We propose that occupancy of SP-activatable receptors on neutrophils triggers two different signal transduction pathways, one being responsible for the generation of signals for oxidase activation and the second, which is independent of Ca2+ and actin signalling, being responsible for priming.
Lloyds
D
D
University Department of Surgery, University of Wales College of Medicine, Cardiff UK.
Hallett
M B
MB
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology*
D000199:Actins; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010088:Oxidoreductases; D002118:Calcium