Involvement of Galanin receptors 1 and 2 in the modulation of mouse vagal afferent mechanosensitivity
It is established that the gut peptide galanin reduces neuronal excitability via GALR1 and GALR3 receptors and increases excitability via 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 all three GALR 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 mechanoesensitivity 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+/+, but this was reversed to potentiation in Galr1-/-, 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.
|Authors||Page, A. J.;Slattery, J. A.;Brierley, S. M.;Jacoby, A. S.;Blackshaw, L. A. :|
|Publisher Name||JOURNAL OF PHYSIOLOGY-LONDON|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17627995|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/2264|