Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa.
It is still unknown which receptors of peripheral sensory pathways encode and integrate an acid-induced nociceptive event in the gastric mucosa. The transient receptor potential vanilloid receptor 1 (TRPV1) and the acid-sensing ion channel 3 (ASIC3) are two nociception-related receptors. Here we investigated (i) to what extent these receptors are distributed in stomach-innervating neurons of dorsal root and nodose ganglia, using immunohistochemistry and retrograde tracing, and (ii) whether their expression is altered in response to a noxious acid challenge of the stomach. We also explored the presence of TRPV1 in the gastric enteric nervous system because of its possible expression by intrinsic sensory neurons. Most stomach-innervating neurons in nodose ganglia were immunoreactive for TRPV1 (80%) and ASIC3 (75%), these results being similar in the dorsal root ganglia (71 and 82%). RT-PCR and Western blotting were performed up to 6 h after oral application of 0.5 m HCl to conscious rats. TRPV1 protein was increased in dorsal root but not in nodose ganglia whereas TRPV1 and ASIC3 mRNAs remained unchanged. TRPV1 mRNA was detected in longitudinal muscle-myenteric plexus preparations of control stomachs and was not altered by the acid challenge. Combined vagotomy and ganglionectomy abolished expression of TRPV1, indicating that it may derive from an extrinsic source. In summary, noxious acid challenge of the stomach increased TRPV1 protein in spinal but not vagal or intrinsic sensory afferents. The TRPV1 receptor may be a key molecule in the transduction of acid-induced nociception of the gastric mucosa and a mediator of visceral hypersensitivity.
Schicho
Rudolf
R
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria. rudolf.schicho@meduni-graz.at
Florian
Waltraud
W
Liebmann
Ingrid
I
Holzer
Peter
P
Lippe
Irmgard Th
IT
D062565:Acid Sensing Ion Channels; D000143:Acids / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015171:Ganglionectomy / Q000379:methods; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014628:Vagotomy / Q000379:methods
C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D000143:Acids; D001572:Benzofurans; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011955:Receptors, Drug; D015222:Sodium Channels; C038675:true blue