TY - JOUR
T1 - Modulation by protein kinase C of the enhanced responsiveness to tachykinins in ovalbumin-sensitized guinea pig alveolar macrophages
AU - Brunelleschi, S.
AU - Guidotto, S.
AU - Tonso, E.
AU - Viano, I.
AU - Fantozzi, R.
N1 - Funding Information:
We wish to thank Dr C. A. Maggi (Menarini Pharmaceuticals, Florence, Italy) for the kind gift of of \[\[3-AlaS-\] NKA(4-10) and MDL 28,564. This work was supported in part by a grant from MURST 60%, 1994.
PY - 1996
Y1 - 1996
N2 - 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 [β-Ala8]-NKA(4-10) dose-dependently increased [3H] phorbor 12, 13 dibutyrate (PDBu) binding to control and sensitized AMs. While fMLP exerted similar effects in both populations, dose-response curves for SP, 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.
AB - 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 [β-Ala8]-NKA(4-10) dose-dependently increased [3H] phorbor 12, 13 dibutyrate (PDBu) binding to control and sensitized AMs. While fMLP exerted similar effects in both populations, dose-response curves for SP, 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.
UR - http://www.scopus.com/inward/record.url?scp=0029817875&partnerID=8YFLogxK
U2 - 10.1016/S0143-4179(96)90071-2
DO - 10.1016/S0143-4179(96)90071-2
M3 - Article
SN - 0143-4179
VL - 30
SP - 249
EP - 260
JO - Neuropeptides
JF - Neuropeptides
IS - 3
ER -