Accommodation and peristalsis are functional responses to obstruction in rat hypertrophic ileum

AIM:To investigate the effects of chronic obstruction on enteric reflexes evoked by electrical stimulation (EFS) or intraluminal distension of the rat hypertrophic ileum.METHODS:Motor responses to EFS and to intraluminal distension were studied in the absence and in the presence of various inhibitors of enteric mediators.Ileum segments from operated (chronic ileal obstruction),sham-operated (control) and normal rats were horizontally mounted,connected to a pressure transducer and intraluminally perfused.The effects of selective serotonin receptor (5-HTR) blockers were investigated on distension-induced responses.The cellular localization of 5-HT3Rs was also examined in control and hypertrophic tissues through confocal microscopy.RESULTS:In non-obstructed segments,EFS elicited tetrodotoxin (TTX)-sensitive responses with high am-plitude contraction followed by weak relaxation.In hypertrophic tissues,EFS lowered the baseline pressure and evoked TTX-sensitive contractions significantly larger than normal (P < 0.01) or control (P < 0.05),and devoid of any relaxation phase (P < 0.01 vs normal).Incubation with atropine and guanethidine [nonadrenergic non-cholinergic (NANC) conditions] did not modify intestinal tone in normal and control preparations,but reversed the accommodation produced by EFS in hypertrophic tissues,and depressed the amplitude of contractions in all types of tissues.L-NAME and α-chymotrypsin blocked residual NANC motility in all tissues and augmented intraluminal pressure in hypertrophic segments (P < 0.05 vs NANC conditions).Intraluminal distension of the intestinal wall evoked non-propulsive cycles of contractions and relaxations in non-obstructed tissues.In all hypertrophic segments,strong propulsive strokes,markedly wider (P < 0.001),and larger than normal (P < 0.001) or control (P < 0.05) were elicited.Both motor patterns were blocked under NANC conditions and with simultaneous incubation with L-NAME and α-chymotrypsin.In all types of tissues,incubation with ketanserin or GR125487 did not modify distension-induced motility.In contrast,blockade of 5-HT3Rs by ondansetron concentration-dependently inhibited motor responses in normal and control tissues,but only slightly impaired enteric reflexes in the hypertrophic preparations.Finally,confocal microscopy did not reveal a different cellular distribution of 5-HT3Rs in control and hypertrophic ileum.CONCLUSION:Accommodation and distension-induced peristalsis of rat hypertrophic ileum are controlled by cholinergic and peptidergic transmission and are negligibly affected by 5-HT3Rs,which modulate distensioninduced motility in non-obstructed tissues.