Galanin and neuropeptide Y reduce cholinergic transmission in the heart of the anaesthetised mouse

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. 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 −1 . This response was attenuated by intravenous administration of GAL (dose ranged from 0.8 to 13 nmol kg −1 ) in a dose‐dependent manner. In GAL‐KO mice, the magnitude of inhibition of the increase in PI (ΔPI) following a bolus dose of GAL was not different from the ΔPI in control mice, and neuropeptide Y (NPY), previously shown to attenuate vagal inhibitory activity in mice, evoked a comparative inhibition of ΔPI in GAL‐KO mice. In GAL‐1R‐KO mice, an intravenous, bolus injection of GAL had no inhibitory effect on vagal activity. 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 ΔPI. The inhibitory effect on ΔPI was reduced in the presence of the NPY Y 2 antagonist, BIIE0246. In GAL‐1R‐KO mice, stimulation of the sympathetic nerve in the presence of propranolol evoked an attenuation of ΔPI 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 ΔPI that followed stimulation of the sympathetic nerve was abolished. 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.British Journal of Pharmacology (2003) 140 , 170–178. doi: 10.1038/sj.bjp.0705404