Characterization of neuropeptide Y receptors mediating contraction, potentiation and inhibition of relaxation.
In addition to its direct vasoconstrictive effect, neuropeptide Y (NPY) potentiates noradrenaline-(NA) induced contraction and inhibits acetylcholine-(ACh) induced relaxation: The aim of the present study was to elucidate the NPY receptor subtypes responsible for mediating these three responses. NPY, peptide YY (PYY) and pro34NPY (a NPY Y1 receptor agonist) induced equipotent and equally strong concentration-dependent contractions of guinea pig basilar arteries. NPY13-36 (a NPY Y2 receptor agonist), however, caused only weak contraction with significantly lower potency. The NPY-induced contraction was significantly inhibited by the selective NPY Y1 receptor antagonist BIBP3226 (1 microM). NPY, PYY and pro34NPY but not NPY13-36 significantly potentiated the NA-induced contraction in guinea pig mesenteric arteries. The potentiation was significantly inhibited by BIBP3226 (1 microM). In precontracted guinea pig basilar arteries, ACh induced a concentration-dependent relaxation which was significantly inhibited by NPY, PYY and NPY13-36 but not by pro34NPY. BIBP3226 had no significant effect on the NPY-induced inhibition of the relaxation. These results suggests that the NPY Y1 receptors mediate the direct contraction and the potentiation of the NA-induced contraction but not the inhibition of the ACh-induced relaxation. This effect seems to be mediated by another NPY receptor subtype, presumably by the Y2 receptor, as judged from the agonist potency order.
Nilsson
T
T
Department of Internal Medicine, Lund University Hospital, Sweden.
You
J
J
Sun
X
X
Hedner
T
T
Edvinsson
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009478:Neuropeptide Y; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; D000109:Acetylcholine; D009638:Norepinephrine