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1 Nerve-Gut Research Laboratory, Hanson Institute, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia
2 Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia
3 Department of Medicine, University of Adelaide, Adelaide, South Australia, 5005, Australia
The neuropeptide galanin is found in the central and peripheral nervous systems. It may have excitatory or inhibitory actions via three subtypes of G-protein-coupled receptor, and it modulates the mechanosensitivity of somatic sensory fibres. We aimed to determine if galanin also modulates vagal afferent mechanosensitivity, and to localize endogenous sources. The responses of ferret and mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated in vitro. The effects of galanin and/or the galanin receptor antagonist galantide on these responses were quantified. Immunohistochemistry for galanin was performed in ferret and mouse proximal stomach and nodose ganglion. In ferrets, retrograde labelling of gastric afferents to the nodose ganglion was combined with immunohistochemistry. When exposed to galanin (1–10 nM), 18/31 ferret and 12/15 mouse gastro-oesophageal afferents (tension, mucosal and tension/mucosal receptors) showed inhibition of mechanosensitivity. Four of 31 ferret afferents showed potentiation of mechanosensitivity, and 9/31 were unaffected (2/15 and 1/15 in mouse, respectively). Galanin effects were reversed after washout or by galantide (10–30 nM). Galantide given alone increased mechanosensitivity. Galanin immunoreactivity was found in nodose neurones, including those innervating the stomach in ferret. Enteric neurones were also galanin immunoreactive, as were endings associated with myenteric ganglia and smooth muscle. We conclude that galanin potently modulates mechanosensitivity of gastro-oesophageal vagal afferents with either facilitatory or inhibitory actions on individual afferent fibres. Both intrinsic and extrinsic (vagal) neurones contain galanin and are therefore potential sources of endogenous galanin.
(Received 8 September 2004;
accepted after revision 23 December 2004;
first published online 6 January 2005)
Corresponding author A. J. Page: Nerve-Gut Research Laboratory, Level 1 Hanson Institute, Frome Road, Adelaide, South Australia 5000, Australia. Email: apage{at}mail.rah.sa.gov.au
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