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Type: Journal article
Title: Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice
Author: Brierley, S.
Carter, R.
Jones III, W.
Xu, L.
Robinson, D.
Hicks, G.
Gebhart, G.
Blackshaw, L.
Citation: The Journal of Physiology, 2005; 567(1):267-281
Publisher: Blackwell Publishing Ltd
Issue Date: 2005
ISSN: 0022-3751
Statement of
Stuart M Brierley, R Carter, W Jones III, Linjing Xu, David R Robinson, Gareth A Hicks, G. F Gebhart and L. Ashley Blackshaw
Abstract: Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here we determined whether these pathways also differ in their chemosensitivity and receptor expression. Using an in vitro mouse colon preparation, individual primary afferents were tested with selective P2X and transient receptor potential vanilloid receptor 1 (TRPV1) receptor ligands. Afferent cell bodies in thoracolumbar and lumbosacral dorsal root ganglia (DRG) were retrogradely labelled from the colon and analysed for P2X3- and TRPV1-like immunoreactivity (LI). Forty per cent of LSN afferents responded to alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP; 1 mm), an effect that was concentration dependent and reversed by the P2X antagonist pyridoxyl5-phosphate 6-azophenyl-2',4'-disulphonic acid (PPADS) (100 microm). Significantly fewer PN afferents (7%) responded to alpha,beta-meATP. Correspondingly, 36% of colonic thoracolumbar DRG neurones exhibited P2X3-LI compared with only 19% of colonic lumbosacral neurones. Capsaicin (3 microm) excited 61% of LSN afferents and 47% of PN afferents; 82% of thoracolumbar and 50% of lumbosacral colonic DRG neurones displayed TRPV1-LI. Mechanically insensitive afferents were recruited by alpha,beta-meATP or capsaicin, and were almost exclusive to the LSN. Capsaicin-responsive LSN afferents displayed marked mechanical desensitization after responding to capsaicin, which did not occur in capsaicin-responsive PN afferents. Therefore, colonic LSN and PN pathways differ in their chemosensitivity to known noxious stimuli and their corresponding receptor expression. As these pathways relay information that may relate to symptoms in functional gastrointestinal disease, these results may have implications for the efficacy of therapies targeting receptor modulation.
Keywords: Lumbosacral Region
Ganglia, Spinal
Neurons, Afferent
Splanchnic Nerves
Mice, Inbred C57BL
Ion Channels
Receptors, Purinergic P2
Adenosine Triphosphate
Antineoplastic Agents
Membrane Potentials
TRPV Cation Channels
Chemoreceptor Cells
Receptors, Purinergic P2X3
DOI: 10.1113/jphysiol.2005.089714
Appears in Collections:Aurora harvest 6
Molecular and Biomedical Science publications

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