C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents

Gregory H. Shen, Lars Grundemar, Zofia Zukowska-Grojec, Rolf Håkanson, Claes R Wahlestedt

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Neuropeptide Y (NPY) is a well-established vasopressor agent present in sympathetic perivascalar nerves. Recently, it was found that high doses of the peptide cause a biphasic pressor-depressor response upon intravenous administration. We now report that C-terminal NPY fragments (NPY-( 18-36) and NPY-(22-36)) given intravenously to conscious or pithed (areflexive) male Sprague-Dawley rats mimic the depressor component of the NPY-(1-36) response while displaying very low pressor activity. Additionally, we have found that the depressor component is blocked by the histamine Hi-antagonist, mepyramine. Since the fragment, NPY-(22-36), was equipotent with NPY in inducing histamine release from isolated peritoneal mast cells, we conclude that short C-terminal NPY fragments, like NPY itself, act on mast cells to initiate histamine-mediated cardiovascular actions. Such actions may conceivably be accounted for by the abundance of positively charged amino acid residues in the C-terminus. Moreover, these fragments have little affinity for vascular NPY receptors, as indicated by their poor ability to displace iodinated NPY or peptide YY (PYY) from specific binding sites on vascular smooth muscle cells derived from rat aorta. In conclusion, we propose that short C-terminal NPY fragments, which contain several positively charged amino acid residues, retain the ability of NPY to release histamine from rat mast cells while being essentially devoid of direct vascular motor activity.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalEuropean Journal of Pharmacology
Volume204
Issue number3
DOIs
StatePublished - Nov 12 1991
Externally publishedYes

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Neuropeptide Y
Mast Cells
Aptitude
Histamine Release
Blood Vessels
Neuropeptide Y Receptors
Peptide YY
Pyrilamine
Amino Acids
Histamine Antagonists
Vasoconstrictor Agents
Vascular Smooth Muscle
Intravenous Administration
Histamine
Smooth Muscle Myocytes
Sprague Dawley Rats
Aorta
Motor Activity
Binding Sites

Keywords

  • Blood pressure
  • Histamine
  • Mast cells
  • Neuropeptide Y
  • Neuropeptide Y fragments
  • Receptor binding

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents. / Shen, Gregory H.; Grundemar, Lars; Zukowska-Grojec, Zofia; Håkanson, Rolf; Wahlestedt, Claes R.

In: European Journal of Pharmacology, Vol. 204, No. 3, 12.11.1991, p. 249-256.

Research output: Contribution to journalArticle

Shen, Gregory H. ; Grundemar, Lars ; Zukowska-Grojec, Zofia ; Håkanson, Rolf ; Wahlestedt, Claes R. / C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents. In: European Journal of Pharmacology. 1991 ; Vol. 204, No. 3. pp. 249-256.
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