In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 293, No. 1 ( 2007-07), p. G121-G127
Abstract:
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 (M 1 ), methoctramine (M 2 ), and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; M 3 ) 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 M 3 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 M 3 receptor antagonism suggests that M 3 receptors may provide specific therapeutic targets in acute radiation enteritis.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00469.2006
Language:
English
Publisher:
American Physiological Society
Publication Date:
2007
detail.hit.zdb_id:
1477329-6
SSG:
12
