Modulation by protein kinase C of the enhanced responsiveness to tachykinins in ovalbumin-sensitized guinea pig alveolar macrophages.
As previously reported, alveolar macrophages (AMs) from ovalbumin-sensitized guinea pigs present an enhanced responsiveness to tachykinins but not to N-formylmethionyl-leucyl-phenylalanine (fMLP). We have investigated the biochemical mechanisms underlying this varied responsiveness to tachykinins. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) induced a larger superoxide anion (O2-) production in AMs from sensitized guinea pigs, as did tachykinins. Pretreatment of AMs with pertussis toxin abolished tachykinin-evoked respiratory burst, had no effect on PMA-evoked O2- production and strongly inhibited fMLP-evoked one, with no appreciable variation between control or sensitized AMs. Staurosporine and its derivative cgp 41251, significantly decreased PMA- and tachykinin-evoked O2- production in both populations, being more potent in control AMs, but exerted little effects against fMLP. Pretreatment of AMs with PMA significantly inhibited fMLP-, PMA- and tachykinin-evoked O2- production in both control and sensitized AMs. fMLP, substance P (SP), neurokinin A (NKA) and the NK2 agonist [beta-Ala8]-NKA(4-10) dose-dependently increased [3H] phorbol 12, 13 dibutyrate (PDBu) binding to control and sensitized AMs. While fMLP exerted similar effects in both populations, dose-response curves for SP1 NKA and the NK2 receptor agonist were shifted leftwards (1, 4 and 3 orders of magnitude, respectively) in sensitized AMs. These results indicate a possible PKC involvement in the enhanced responsiveness to tachykinins in actively sensitized AMs.
Brunelleschi
S
S
Department of Medical Sciences, University of Turin, Novara, Italy.
Guidotto
S
S
Tonso
E
E
Viano
I
I
Fantozzi
R
R
D000818:Animals; D001886:Bordetella pertussis / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007114:Immunization; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D018039:Receptors, Tachykinin / Q000187:drug effects / Q000378:metabolism*; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015320:Tachykinins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013481:Superoxides; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015288:Neurokinin A; D010047:Ovalbumin; D011493:Protein Kinase C; D019311:Staurosporine; C059539:midostaurin; D013755:Tetradecanoylphorbol Acetate