Impaired gastrocolonic response and peristaltic reflex in slow-transit constipation: role of 5-HT(3) pathways.
Colonic motility is modulated by the 5-hydroxytryptamine (5-HT)(3)-dependent gastrocolonic response and 5-HT(3)-independent peristaltic reflex. We compared descending colon tone responses to antral distension, duodenal lipid perfusion, and colonic distension after double-blind placebo or granisetron in 13 healthy volunteers and nine slow-transit constipated patients. Antral distension (100-300 ml) and duodenal lipids (3 kcal/min) evoked increases in colon tone in volunteers, which were blunted in constipated patients (P < 0.05). Granisetron (10 microg/kg) reduced responses to antral distension and lipids in volunteers and to lipids in constipated patients (P < 0.05). The ascending contraction of the peristaltic reflex was blunted in constipated patients (P < 0.05), whereas descending responses were similar. Granisetron did not modify the peristaltic reflex. Colonic responses to bethanechol were similar in patients and volunteers. In conclusion, antral distension- and duodenal lipid-activated gastrocolonic responses and ascending contractions of the peristaltic reflex are impaired with slow-transit constipation with loss of both 5-HT(3)-dependent and -independent function. Thus abnormalities of neural reflex modulation of colonic motor function may play pathophysiological roles in slow-transit constipation.
Division of Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, S-41345 Gothenburg, Sweden.
Einar S
ES
Björnsson
William D
WD
Chey
Forrest
F
Hooper
Michelle L
ML
Woods
Chung
C
Owyang
William L
WL
Hasler
D000328:Adult; D018723:Bethanechol / Q000494:pharmacology; D002404:Catheterization; D002908:Chronic Disease; D003106:Colon / Q000187:drug effects / Q000503:physiopathology*; D003248:Constipation / Q000503:physiopathology*; D004386:Duodenum; D005260:Female; D005772:Gastrointestinal Transit; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009129:Muscle Tonus; D009130:Muscle, Smooth / Q000187:drug effects; D010528:Peristalsis; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012018:Reflex; D013270:Stomach / Q000503:physiopathology*
D008055:Lipids; D018721:Muscarinic Agonists; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D018723:Bethanechol