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Characterization of vascular neuropeptide Y receptors
Author(s) -
Grundemar Lars,
Jonas S.E.,
Mörner N.,
Högestätt Edward D.,
Wahlestedt Claes,
Håkanson Rolf
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14208.x
Subject(s) - neuropeptide y receptor , receptor , neuropeptide , neuroscience , biology , chemistry , medicine
1 In the present study we compared neuropeptide Y (NPY) and NPY‐related analogues for their ability to activate or bind to vascular NPY receptors in four experimental set‐ups. Previous results have suggested the existence of different receptor subtypes, Y 1 receptors requiring full‐length NPY (1–36) or [Pro 34 ]‐NPY, and Y 2 receptors recognizing also N‐terminally truncated forms of NPY but not [Pro 34 ]‐NPY. 2 NPY 1–36 and [Pro 34 ]‐NPY dose‐dependently increased arterial pressure in the anaesthetized rat with a similar magnitude and potency. NPY 2–36 was much less potent than NPY 1–36. NPY 4–36 and NPY 11–36 were inactive even at a dose as high as 10 nmol kg −1 . 3 NPY 1–36, [Pro 34 ]‐NPY, NPY 2–36 and NPY 5–36 concentration‐dependently increased the coronary resistance in the Langendorff preparation of the rat. NPY 1–36 and [Pro 34 ]‐NPY were equipotent, while NPY 2–36 and NPY 5–36 were about 7 and 20 times less potent. At 0.3 μ m , NPY 11–36, NPY 20–36 and NPY 22–36 induced a slight contraction while NPY 23–36 was inactive. 4 NPY 1–36, [Pro 34 ]‐NPY, NPY 2–36, NPY 4–36, NPY 5–36 and NPY 11–36 evoked concentration‐dependent contractions in the isolated inferior caval vein of the rat and guinea‐pig. [Pro 34 ]‐NPY was more potent than NPY 1–36. NPY 2–36 was equipotent with NPY 1–36, while NPY 4–36, NPY 5–36 and NPY 11–36 were approximately 30 times less potent. 5 [Pro 34 ]‐NPY was equipotent with NPY 1–36 in displacing the 125 I‐labelled gut hormone peptide ([ 125 I]‐PYY) from rat aortic smooth muscle cells, while NPY 2–36 and shorter forms of NPY were much less potent or inactive. 6 In caval vein smooth muscle cells of the rat, the displacement pattern was more complex than in aortic smooth muscle cells, in that both [Pro 34 ]‐NPY and NPY 13–36 effectively displaced the radioligand, albeit none of them completely. 7 In conclusion, the NPY‐evoked pressor response in the whole rat and coronary vessels seems to be mediated by vascular Y 1 receptors and the binding characteristics of the NPY‐related peptides in the aortic smooth muscle cells correspond to a population of such receptors. In the caval vein, the profile of the bioactivity and the binding affinity of the NPY‐related peptides suggest a mixed population of Y 1 /Y 2 receptors.