Neuropeptide Y inhibits double peaked vasoconstrictor responses to periarterial nerve stimulation primarily through prejunctional Y2 receptor subtype in canine splenic arteries.
1 The effects of BIIE 0246, a novel and non-peptide neuropeptide Y (NPY) Y2 receptor antagonist on sympathetic vasoconstriction of the canine splenic artery were investigated. 2 The vasoconstrictor response to periarterial electrical nerve stimulation was described to be a double peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor-mediated constriction followed by a prolonged, mainly alpha1 adrenoceptor-induced response. 3 BIIE 0246 at a concentration of 0.1-1 microM dose-dependently potentiated double peaked constrictions at low frequencies (1 and 4 Hz), whereas at high frequency (10 Hz), it failed to affect these responses. BIIE 0246 (1 microM) also enhanced double peaked responses even in the presence of rauwolscine (0.1 microM). NPY (13-36) (1-100 nM), a selective Y2 receptor agonist reduced these two peaked responses in a dose-related manner. The vasoconstriction to noradrenaline (0.1-10 nmol) or adenosine triphosphate (0.01-1 micromol) was not significantly influenced by either 1 microM BIIE 0246 or 100 nM NPY (13-36). Exposure of tissues to 1 microM BIIE 0246 almost completely prevented the suppression of double peaked constrictions by NPY (13-36) (10 nM) or by NPY (10 nM). 4 We conclude that NPY inhibits sympathetic purinergic and adrenergic vasoconstrictions through an activation of prejunctional Y2 receptor subtype in the neurovascular junction of the canine splenic artery.
Yang
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Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Chiba
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013157:Splenic Artery / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D001552:Benzazepines; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246