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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/G121    most recent 00469.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 Frisby, C. L. Articles by Blackshaw, L. A. Search for Related Content PubMed PubMed Citation Articles by Frisby, C. L. Articles by Blackshaw, L. A.

NEUROREGULATION AND MOTILITY

Roles of muscarinic receptor subtypes in small intestinal motor dysfunction in acute radiation enteritis

¹Discipline of Medicine and ²Discipline of Physiology, University of Adelaide, and ³Department of Radiation Oncology and ⁴Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, South Australia

Submitted 11 October 2006 ; accepted in final form 2 May 2007

Administration of abdominal radiotherapy results in small intestinal motor dysfunction. We have developed a rat radiation enteritis model that, after exposure in vivo, shows high-amplitude, long-duration (HALD) pressure waves in ex vivo ileal segments. These resemble in vivo dysmotility where giant contractions migrate both antegradely and retrogradely. Mediation of these motor patterns is unclear, although enteric neural components are implicated. After the induction of acute radiation enteritis in vivo, ileal segments were isolated and arterially perfused. TTX, hexamethonium, atropine, or the selective muscarinic antagonists pirenzepine (M₁), methoctramine (M₂), and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; M₃) were added to the perfusate. The baseline mean rate per minute per channel of HALD pressure waves was 0.35 ± 0.047. This was significantly reduced by TTX (83.3%, P < 0.01), hexamethonium (90.3%, P < 0.03), and atropine (98.4%, P < 0.01). The HALD pressure wave mean rate per minute per channel was significantly reduced by pirenzepine (81.1%, P < 0.03), methoctramine (96.8%, P < 0.001), and 4-DAMP (93.1%, P < 0.03) compared with predrug baseline data. As an indicator of normal motility patterns, the frequency of low-amplitude, short-duration pressure waves was also assessed. The mean rate per minute per channel of 5.15 ± 0.98 was significantly increased by TTX (19%, P < 0.05) but significantly reduced by pirenzepine (35.1%, P < 0.02) and methoctramine (75%, P < 0.0003). However, the rate of small-amplitude pressure waves was not affected by hexamethonium, atropine, or the M₃ antagonist 4-DAMP. The data indicate a role for neuronal mechanisms and the specific involvement of cholinergic receptors in generating dysmotility in acute radiation enteritis. The effect of selective M₃ receptor antagonism suggests that M₃ receptors may provide specific therapeutic targets in acute radiation enteritis.

radiation enteritis; high-amplitude contractions