Increased acid-sensing ion channel ASIC-3 in inflamed human intestine.
OBJECTIVE
Acid-sensing ion channels (ASICs) are expressed by rat sensory neurons and may mediate pain associated with tissue acidosis after inflammation or injury. Our aim was to examine the molecular forms and localization of ASICs in human intestine and dorsal root ganglia using immunochemical techniques, and to measure the effects of inflammation and injury.


METHODS
Inflamed Crohn's disease intestine and injured human dorsal root ganglia, with appropriate controls, were studied by Western blotting and immunohistochemistry, using specific affinity-purified ASIC antibodies.


RESULTS
In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers. There was a corresponding trend for an increased immunoreactive density and increased number of ASIC-3-positive neurons in the myenteric and sub-mucous plexus of inflamed intestine. In dorsal root ganglia, immunoreactivity for all ASICs was restricted to a sub-population (about 50%) of small-diameter (nociceptor) sensory neurons, and was generally less intense after injury.


CONCLUSIONS
Increased ASIC-3 in inflamed intestine suggests a role in pain or dysmotility, for which ASICs represent new therapeutic targets.
Yiangou
Y
Y
Peripheral Neuropathy Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Facer
P
P
Smith
J A
JA
Sangameswaran
L
L
Eglen
R
R
Birch
R
R
Knowles
C
C
Williams
N
N
Anand
P
P
D062565:Acid Sensing Ion Channels; D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005727:Ganglia, Spinal / Q000737:chemistry* / Q000293:injuries; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007422:Intestines / Q000737:chemistry* / Q000294:innervation / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009197:Myenteric Plexus / Q000737:chemistry; D009419:Nerve Tissue Proteins; D015222:Sodium Channels / Q000032:analysis*; D013368:Submucous Plexus / Q000737:chemistry
C568266:ASIC1 protein, human; C112231:ASIC3 protein, human; C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels