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

Erlinge, David LU ; Edvinsson, Lars LU ; Brunkwall, Jan; Yee, Frances and Wahlestedt, Claes (1993) In European Journal of Pharmacology 240(1). p.77-80
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), corresponding to the human Y1 receptor NH2-terminus, was incubated with segments of human subcutaneous arteries and veins for 48 h at 37 degrees 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... (More)
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), corresponding to the human Y1 receptor NH2-terminus, was incubated with segments of human subcutaneous arteries and veins for 48 h at 37 degrees 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Neuropeptide Y, Blood vessel (human), Antisense, Neuropeptide Y Y1 receptor
in
European Journal of Pharmacology
volume
240
issue
1
pages
77 - 80
publisher
Elsevier
external identifiers
  • pmid:8405124
  • scopus:0027281604
ISSN
1879-0712
DOI
10.1016/0014-2999(93)90548-V
language
English
LU publication?
yes
id
505c414d-afca-434f-925c-d78e8a6f8525 (old id 1107192)
date added to LUP
2008-07-30 12:48:48
date last changed
2017-04-30 08:54:19
@article{505c414d-afca-434f-925c-d78e8a6f8525,
  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), corresponding to the human Y1 receptor NH2-terminus, was incubated with segments of human subcutaneous arteries and veins for 48 h at 37 degrees 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.},
  author       = {Erlinge, David and Edvinsson, Lars and Brunkwall, Jan and Yee, Frances and Wahlestedt, Claes},
  issn         = {1879-0712},
  keyword      = {Neuropeptide Y,Blood vessel (human),Antisense,Neuropeptide Y Y1 receptor},
  language     = {eng},
  number       = {1},
  pages        = {77--80},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Human neuropeptide Y Y1 receptor antisense oligodeoxynucleotide specifically inhibits neuropeptide Y-evoked vasoconstriction},
  url          = {http://dx.doi.org/10.1016/0014-2999(93)90548-V},
  volume       = {240},
  year         = {1993},
}