Human neuropeptide Y Y1 receptor antisense oligodeoxynucleotide specifically inhibits neuropeptide Y-evoked vasoconstriction.
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.
Erlinge
D
D
Department of Internal Medicine, Lund University, Sweden.
Edvinsson
L
L
Brunkwall
J
J
Yee
F
F
Wahlestedt
C
C
D001483:Base Sequence; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D009478:Neuropeptide Y; D016376:Oligonucleotides, Antisense; D017476:Receptors, Neuropeptide Y