Structural requirements for neuropeptide Y in mast cell and G protein activation.
Incubation of neuropeptide Y or its C-terminal fragments with rat peritoneal mast cells resulted in a dose-dependent histamine release. Fragment 18-36 of neuropeptide Y was the most biologically active peptide. EC25 value on rat mast cells was 7.2 +/- 2.2 nM. Neuropeptide Y was also able to induce a flare response after intradermal injection in humans. The histamine releasing effects of neuropeptide Y related peptides were greatly inhibited by pretreatment of rat mast cells with pertussis toxin or benzalkonium chloride. Neuropeptide Y and C-terminal related peptides also stimulated the GTPase activity of purified heterotrimeric G proteins in a dose-dependent manner from 1 to 50 microM. Binding studies with [125I]neuropeptide Y were unable to provide evidence for the presence of specific binding sites on the surface of mast cells. The alpha helical conformation of neuropeptide Y fragments was studied by measuring the circular dichroism spectra. Neuropeptide Y-(18-36) was the smallest fragment having a strong helical conformation. Our results demonstrate that neuropeptide Y activates mast cells through a non-specific process leading to G protein activation.
Mousli
M
M
INSERM U 425, Université Louis Pasteur, Strasbourg I, Illkirch, France.
Trifilieff
A
A
Pelton
J T
JT
Gies
J P
JP
Landry
Y
Y
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013329:Structure-Activity Relationship
D009478:Neuropeptide Y; D010446:Peptide Fragments; D019204:GTP-Binding Proteins