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Characterization of neuropeptide Y (NPY) receptors in human cerebral arteries with selective agonists and the new Y 1 antagonist BIBP 3226
Author(s) -
Abounader Roger,
Villemure JeanGuy,
Hamel Edith
Publication year - 1995
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.1476-5381.1995.tb15060.x
Subject(s) - endocrinology , neuropeptide y receptor , medicine , agonist , peptide yy , vasoconstriction , receptor , chemistry , antagonist , biology , neuropeptide
1 We have characterized pharmacologically the receptor subtype(s) responsible for the neuropeptide Y (NPY)‐induced vasoconstriction in human cerebral arteries. NPY, PYY and several of their derivatives with well defined affinities at the known Y 1 and Y 2 receptor subtypes were used. Moreover, we tested the ability of the new Y 1 receptor antagonist, BIBP 3226, to antagonize the NPY‐induced cerebral vasoconstriction. 2 NPY, PYY and their agonists with high affinities at the Y 1 receptor subtype ([Leu 31 ‐Pro 34 ]‐NPY and [Leu 31 ‐Pro 34 ]‐PYY) elicited strong, long lasting and concentration‐dependent contractions of human cerebral arteries. Compounds with Y 2 affinity such as PYY 3–36 or NPY 13–36 either elicited a submaximal contraction at high concentrations or failed to induce any significant vasomotor response. Also, the application of NPY or the specific Y 1 agonist, [Leu 31 ‐Pro 34 ]‐NPY, to human cerebral vessels pretreated with the Y 1 agonist, NPY 13–36 , resulted in contractile responses identical to those obtained when these compounds were tested without prior application of NPY 13–36 . 3 The order of agonist potency at the human cerebrovascular receptor was: [Leu 31 ‐Pro 34 ]‐NPY= [Leu 31 ‐Pro 34 ]‐PYY≤NPY>PYY>PYY 3–36 > > >NPY 13–36 , which corresponded to that reported previously at the neuronal and vascular Y 1 receptors. 4 Increasing concentrations (10 −9 ‐10 −6 m ) of the Y 1 receptor antagonist, BIBP 3226, to human cerebral vessels caused a parallel and rightward shift in the NPY dose‐response curves without any significant change in the maximal contractile response. The calculated pA 2 was 8.52±0.13, a value compatible with the reported affinity at the rodent and human Y 1 receptor. 5 We conclude that Y 1 receptors exclusively, mediate the NPY‐induced contraction in human cerebral arteries and we show that BIBP 3226 is a potent and competitive antagonist of this Y 1 ‐mediated vasoconstriction.