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

Erlinge, David LU orcid ; 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)
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author
; ; ; and
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
2016-04-01 12:15:51
date last changed
2024-01-08 14:13:29
@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}},
  keywords     = {{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}},
  doi          = {{10.1016/0014-2999(93)90548-V}},
  volume       = {{240}},
  year         = {{1993}},
}