1 This study investigated the eects of BIIE0246, a novel neuropeptide Y (NPY) Y 2 receptor antagonist, on the inhibition of cholinergic neuroeector transmission in rat heart and guinea-pig trachea and purinergic neuroeector transmission in guinea-pig vas deferens produced by the NPY Y 2 receptor agonist, N-acetyl [Leu 28,31 ] NPY 24-36. 2 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 ] NPY 24-36 but had no eect when applied alone. 6 The ®ndings support the view that the nerve terminals of postganglionic parasympathetic and sympathetic neurones possess neuropeptide Y Y 2 receptors which, when activated, reduce neurotransmitter release.

1 This study investigated the effects of galanin (GAL) on inhibition of cholinergic (vagal) activity in the mouse heart using control galanin knockout (GAL-KO) and GAL-1R receptor knockout (GAL-1R-KO) mice. 2 In pentobarbitone anaesthetised mice, supramaximal stimulation every 30 s of the vagus nerve innervating the heart, increased pulse interval (PI) by approximately 50 ms or decreased heart rate by approximately 100 beats min À1. This response was attenuated by intravenous administration of GAL (dose ranged from 0.8 to 13 nmol kg À1 ) in a dose-dependent manner. 3 In GAL-KO mice, the magnitude of inhibition of the increase in PI (DPI) following a bolus dose of GAL was not different from the DPI in control mice, and neuropeptide Y (NPY), previously shown to attenuate vagal inhibitory activity in mice, evoked a comparative inhibition of DPI in GAL-KO mice. 4 In GAL-1R-KO mice, an intravenous, bolus injection of GAL had no inhibitory effect on vagal activity. 5 In control mice, stimulation of the sympathetic nerve at 25 V, 10 Hz for 2 min in the presence of propranolol evoked a long-lasting attenuation of DPI. The inhibitory effect on DPI was reduced in the presence of the NPY Y 2 antagonist, BIIE0246. 6 In GAL-1R-KO mice, stimulation of the sympathetic nerve in the presence of propranolol evoked an attenuation of DPI not significantly different from the response in control mice in the presence of BIIE0246. Following administration of BIIE0246 in GAL-1R-KO mice, the inhibition of DPI that followed stimulation of the sympathetic nerve was abolished. 7 These findings support the view that the nerve terminals of parasympathetic neurons in the mouse heart possess both GAL-1R and NPY Y 2 receptors which, when activated, reduce acetylcholine release.

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