Work

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

Year: 1993

Type: article

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.

Source: European Journal of Pharmacology

DOI: 10.1016/0014-2999(93)90548-v

Authors: David Erlinge, Lars Edvinsson, Jan Brunkwall, Frances Yee, Claes Wahlestedt

Institutions: Lund University, Cornell University

Language: English

Topic: Neuropeptides and Animal Physiology

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,230