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- Title
Adenosine 2B receptors (A<sub>2B</sub>AR) on enteric neurons regulate murine distal colonic motility.
- Authors
Chandrasekharan, Bindu P.; Kolachala, Vasantha L.; Dalmasso, Guillaume; Merlin, Didier; Ravid, Katya; Sitaraman, Shanthi V.; Srinivasan, Shanthi
- Abstract
Delayed colonic emptying leading to constipation is a significant health concern. We investigated the role of adenosine 2B receptor (A2BAR) in modulating distal colonic motility using wild-type and A2BAR-knockout (A2BAR-/-) mice. Colon motility was assessed using stool characteristics and colonic transit. Distal colonic ganglia, isolated by laser capture micro-dissection, were tested for A2BAR expression by RT-PCR. The distal colon contraction and relaxation responses were assessed by electrical field stimulation (EFS) in presence of A2BAR agonists, antagonists or inhibitors of nitric oxide (NO) and guanylate cyclase. Nitrite levels were measured in enteric neuronal cultures exposed to A2BAR agonists/antagonists. A2BAR-/- mice display increased stool retention, decreased stool frequency, delayed colonic emptying, and decreased circular muscle relaxation. RT-PCR identified A2BAR expression in distal colonic ganglia. EFS studies revealed that enteric neuronal A2BAR is essential for distal colonic relaxation, and A2BAR antagonists can inhibit relaxation. Enteric neurons stimulated with A2BAR agonists produced more nitrite than cultures treated with antagonists. We demonstrate an essential role of A2BAR in regulating distal colon relaxation, as A2BR activation is linked to NO signaling, Hence targeting the colonic A2BAR could represent a novel therapeutic strategy to treat constipation.
- Subjects
ADENOSINES; CONSTIPATION; DEFECATION disorders; MOTILITY of the colon; ENTERIC nervous system; NEURONS
- Publication
FASEB Journal, 2009, Vol 23, Issue 8, p2727
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.09-129544