Effects of a selective neuropeptide Y Y2 receptor antagonist BIIE0246 on Y2 receptors at peripheral neuroeffector junctions

摘要

class="enumerated" style="list-style-type:decimal">This study investigated the effects of BIIE0246, a novel neuropeptide Y (NPY) Y2 receptor antagonist, on the inhibition of cholinergic neuroeffector transmission in rat heart and guinea-pig trachea and purinergic neuroeffector transmission in guinea-pig vas deferens produced by the NPY Y2 receptor agonist, N-acetyl [Leu^28,31] NPY 24-36.In pentobarbitone anaesthetized rats, supramaximal stimulation every 30 s, of the vagus nerve innervating the heart, increased pulse interval by approximately 100 ms. This response was attenuated by intravenous administration of N-acetyl [Leu^28,31] NPY 24-36 (10 nmol kg⁻¹).Transmural stimulation of segments of guinea-pig trachea at 1 min intervals with 5 s trains of stimuli at 0.5, 5, 10, 20 and 40 Hz evoked contractions which were reduced in force by N-acetyl [Leu^28,31] NPY 24-36 (2 μM).In guinea-pig vasa deferentia, the amplitude of excitatory junction potentials evoked by trains of 20 stimuli at 1 Hz was reduced in the presence of N-acetyl [Leu^28,31] NPY 24-36 (1 μM).In all preparations BIIE0246 attenuated the inhibitory effect of N-acetyl [Leu^28,31] NPY 24-36 but had no effect when applied alone.The findings support the view that the nerve terminals of postganglionic parasympathetic and sympathetic neurones possess neuropeptide Y Y2 receptors which, when activated, reduce neurotransmitter release.