Structural requirements for neuropeptide Y in mast cell and G protein activation

European Journal of Pharmacology
M MousliY Landry

Abstract

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.

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Citations

May 4, 2001·European Journal of Pharmacology·R E MalmströmM Sjölander
Jan 16, 2002·European Journal of Pharmacology·Xavier Ferry, Yves Landry
Jul 11, 2002·European Journal of Pharmacology·Rickard E Malmström
Nov 21, 1996·European Journal of Pharmacology·E CzerwiecP M Vanderheyden
May 23, 1998·European Journal of Pharmacology·A ChahdiY Landry
Nov 10, 1998·The Journal of General Physiology·D LorenzM Bienert
May 5, 1998·Fundamental & Clinical Pharmacology·A ChahdiY Landry
Sep 1, 1996·Trends in Pharmacological Sciences·J M LundbergR E Malmström
Jun 29, 2004·Pulmonary Pharmacology & Therapeutics·David A GronebergAxel Fischer
Jan 27, 2018·International Journal of Molecular Sciences·Susanne Grässel, Dominique Muschter
Dec 1, 2001·Biological & Pharmaceutical Bulletin·M YoshidaK Takagi
May 15, 2013·American Journal of Hematology·Pamela GhoshJose A Halperin
Jun 30, 2006·The Journal of Pharmacology and Experimental Therapeutics·Iain R ToughHelen M Cox
Oct 12, 2000·Journal of Cardiovascular Pharmacology·R E MalmströmJ Weilitz
Mar 28, 2001·Annals of the New York Academy of Sciences·M Levite

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