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Thirdly, the GalR1 receptor is localised on intrinsic cholinergic neurons at the sinoatrial node. Like neuropeptide-Y, exogenous galanin reduces vagal bradycardia via a pre-synaptic pathway involving a reduction in acetylcholine release that is GalR1 receptor mediated and protein kinase C dependent. Finally, there does not appear to be any cross reactivity between neuropeptide-Y and galanin in terms of their respective membrane receptors as Y2 receptor inhibition does not alter the inhibitory action of galanin and GalR1 inhibition does not alter the inhibitory action of neuropeptide-Y. We demonstrated that sympathetic neurons from freshly dissected left and right stellate ganglia contain mRNA for galanin although tyrosine hydroxylase. However, following dissociation and 3?days of culture, most sympathetic neurons from both ganglia express galanin. This is an interesting finding and may represent an injury response as local cardiac galanin expression is also increased in a rat model post myocardial infarction [37] driven by sympathetic hyperactivity [38]. Whether excess galanin production contributes to impaired vagal neurotransmission in this context remains to be shown. We also demonstrated the release of both neuropeptide-Y and galanin into the tissue perfusate following sympathetic stimulation, however significantly more neuropeptide-Y was released than galanin. The peak perfusate concentrations (20�C30?pM over 20?min post 2?minute sympathetic stimulation) were significantly less than the concentrations of exogenous peptide required to significantly reduce vagal bradycardia (50?nM and above, over a 10?min incubation period, although there was a trend for a reduction in vagal bradycardia even at the lowest 5?nM dose used) as is observed with many neurotransmitters and bioassays. Given localised metabolism, re-uptake and diffusion, neither are likely to accurately reflect the exact concentration of peptide released locally at the level of the neuron within the atrial tissue. Instead, the dose response curve experiments should be viewed as proof of principle that exogenous galanin can reduce vagal bradycardia. Our perfusate concentrations were higher than those mean values observed in human plasma (e.g. galanin 4�C6?pM [39], neuropeptide-Y 18?pM [40]) but lower than those of neuropeptide-Y collected from coronary venous sinus blood sampling immediately after cardiac sympathetic stimulation (peaking at 1?nM after 3?min of sympathetic stimulation at 10?Hz [20]).