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This Article Full Text Full Text (PDF) All Versions of this Article: 583/2/719    most recent jphysiol.2007.136838v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lomax, A. E. Articles by Vanner, S. J. Search for Related Content PubMed PubMed Citation Articles by Lomax, A. E. Articles by Vanner, S. J. Related Collections Alimentary

¹ Gastrointestinal Diseases Research Unit and Departments of Physiology and Medicine, Queen's University, Kingston, Ontario, Canada K7L 5G2

Recent studies suggest that altered neural regulation of the gastrointestinal microvasculature contributes to the pathogenesis of inflammatory bowel disease. Therefore, we employed video microscopy techniques to monitor nerve-evoked vasoconstrictor responses in mouse colonic submucosal arterioles in vitro and examined the effect of 2,4,6-trinitrobenzene sulphonic acid (TNBS) colitis. Nerve stimulation (2–20 Hz) caused frequency-dependent vasoconstrictor responses that were abolished by tetrodotoxin (300 nM) and guanethidine (10 µM). The P2 receptor antagonist suramin (100 µM) or the ₁-adrenoceptor antagonist prazosin (100 nM) reduced the vasoconstriction and the combination of suramin and prazosin completely abolished responses. Nerve-evoked constrictions of submucosal arterioles from mice with TNBS colitis were inhibited by prazosin but not suramin. Superfusion of ATP (10 µM) resulted in large vasoconstrictions in control mice but had no effect in mice with colitis whereas constrictions to phenylephrine (3 µM) were unaffected. P2X₁ receptor immunohistochemistry did not suggest any alteration in receptor expression following colitis. However, Western blotting revealed that submucosal P2X₁ receptor expression was increased during colitis. In contrast to ATP, β-methylene-ATP (1 µM), which is resistant to catabolism by nucleotidases, constricted control and TNBS arterioles. This indicates that reduced purinergic transmission to submucosal arterioles may be due to increased degradation of ATP during colitis. These data comprise the first description of the neural regulation of mouse submucosal arterioles and identify a defect in sympathetic regulation of the GI vasculature during colitis due to reduced purinergic neurotransmission.

(Received 18 May 2007; accepted after revision 26 June 2007; first published online 5 July 2007)
Corresponding author A. E. Lomax: Gastrointestinal Diseases Research Unit, Queen's University at Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada. Email: lomaxa{at}post.queensu.ca