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J Physiol Volume 583, Number 2, 675-684, September 1, 2007 DOI: 10.1113/jphysiol.2007.135939
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NEUROSCIENCE

Involvement of galanin receptors 1 and 2 in the modulation of mouse vagal afferent mechanosensitivity

 Amanda J. Page1,2,3, James A. Slattery1,3, Stuart M. Brierley1,3, Arie S. Jacoby4 and L. Ashley Blackshaw1,2,3

1 Nerve Gut Research Laboratory, Department of Gastroenterology and Hepatology, Hanson Institute, Royal Adelaide Hospital
2 Department of Medicine
3 Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, Australia
4 Neurobiology Program, Garvan Institute of Medical Research, Sydney, Australia

It is established that the gut peptide galanin reduces neuronal excitability via galanin receptor subtypes GALR1 and GALR3 and increases excitability via subtype GALR2. We have previously shown that galanin potently reduces mechanosensitivity in the majority of gastro-oesophageal vagal afferents, and potentiates sensitivity in a minority. These actions may have implications for therapeutic inhibition of gut afferent signalling. Here we investigated which galanin receptors are likely to mediate these effects. We performed quantitative RT-PCR on RNA from vagal (nodose) sensory ganglia, which indicated that all three GALR subtypes were expressed at similar levels. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of galanin receptor ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors which respond only to mucosal stroking. Galanin induced potent inhibition of mechanosensitivity in both types of afferents. This effect was totally lost in mice with targeted deletion of Galr1. The GALR1/2 agonist AR-M961 caused inhibition of mechanosensitivity in Galr1+/+ mice, but this was reversed to potentiation in Galr1–/– mice, indicating a minor role for GALR2 in potentiation of vagal afferents. We observed no functional evidence of GALR3 involvement, despite its expression in nodose ganglia. The current study highlights the complex actions of galanin at different receptor subtypes exhibiting parallels with the function of galanin in other systems.

(Received 7 May 2007; accepted after revision 12 July 2007; first published online 12 July 2007)
Corresponding author A. J. Page: Nerve Gut Research Laboratory, Level 1 Hanson Institute, Frome Road, Adelaide, SA 5000, Australia. Email: amanda.page{at}health.sa.gov.au

A. Page and J. Slattery contributed equally to this work.






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