Human neuropeptide Y Y1 receptor antisense oligodeoxynucleotide specifically inhibits neuropeptide Y-evoked vasoconstriction

David Erlinge, Lars Edvinsson, Jan Brunkwall, Frances Yee, Claes R Wahlestedt

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

This paper describes a new approach for the development of an inhibitor of the contractile responses of neuropeptide Y in human blood vessels by the use of an antisense oligodeoxynucleotide complementary to human neuropeptide Y Y1 receptor mRNA. One micromolar of an antisense 18-base oligodeoxynucleotide (hY1-AS), correspondeng to the human Y1 receptor NH2-terminus, was incubated with segments of human subcutaneous arteries and veins for 48 h at 37°C. Control vessels were incubated with the corresponding sense oligodeoxynucleotide (hY1-S) or a 3-base mismatched antisense oligodeoxynucleotide (hY1-MM) or no oligodeoxynucleotide. The contractile response to neuropeptide Y was markedly attenuated in both arteries and veins after treatment with hY1-AS, but was unaffected by hY1-S or hY1-MM. The pD2 values, i.e. the potency of neuropeptide Y, did not differ in hY1-AS treated vessels, suggesting a non-competitive receptor interaction as a result of down-regulation of Y1 receptors. Responses to noradrenaline or high K+ were unaffected by hY1-AS. This study may represent a new and highly specific approach to vascular pharmacology.

Original languageEnglish
Pages (from-to)77-80
Number of pages4
JournalEuropean Journal of Pharmacology
Volume240
Issue number1
DOIs
StatePublished - Aug 10 1993
Externally publishedYes

Fingerprint

Oligodeoxyribonucleotides
Neuropeptide Y
Vasoconstriction
Blood Vessels
Veins
Arteries
Norepinephrine
Down-Regulation
neuropeptide Y-Y1 receptor
Pharmacology
Messenger RNA

Keywords

  • Antisense
  • Blood vessel (human)
  • Neuropeptide Y
  • Neuropeptide Y Y receptor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Human neuropeptide Y Y1 receptor antisense oligodeoxynucleotide specifically inhibits neuropeptide Y-evoked vasoconstriction. / Erlinge, David; Edvinsson, Lars; Brunkwall, Jan; Yee, Frances; Wahlestedt, Claes R.

In: European Journal of Pharmacology, Vol. 240, No. 1, 10.08.1993, p. 77-80.

Research output: Contribution to journalArticle

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