Effect of somatostatin on gastrointestinal contractility in Schistosoma mansoni infected mice.
Schistosoma mansoni infection induces severe gastrointestinal motility disturbances which are characterised by hyperactivity of intestinal muscle, abdominal pain, diarrhoea, vomiting and nausea. During schistosomiasis, the neuropeptide somatostatin is generated within inflammatory granulomas. However, somatostatin is also an important inhibitory modulator of gastrointestinal motility. In the present study, we have investigated the potential of somatostatin to reduce schistosomiasis-induced hyperactivity of gastrointestinal smooth muscle. Organ bath experiments were performed to study the contractility of isolated smooth muscle strips of intestine from control mice and from mice that were infected with S. mansoni for 2, 4, 8 and 16 weeks. Electrical field stimulation (0.5-8 Hz) of enteric nerves induced frequency-dependent neurogenic contractions of cholinergic origin in all regions of the small intestine. Somatostatin (0.1-1 microM) concentration-dependently inhibited the contractions to enteric nerve stimulation in the small intestine from uninfected control mice and from acutely S. mansoni infected mice (2 and 4 weeks of infection). After 8 weeks of infection with S. mansoni, this inhibitory effect of somatostatin was less pronounced and after 16 weeks of infection it was completely abolished. Histology demonstrated that chronic infection of mice with S. mansoni was associated with significant alterations in the musculature of the small intestine. These alterations may be associated with physiological changes in the responsiveness to somatostatin and suggest that the somatostatin neuroregulatory circuit of enteric neurotransmission in the small intestine is disturbed during chronic schistosomiasis mansoni.
Division of Gastroenterology, Faculty of Medicine, Room T2.05, University of Antwerp, Universiteitsplein 1, Wilrijk, Belgium.
Joris G
JG
De Man
Shyama
S
Chatterjee
Benedicte Y
BY
De Winter
Gunther
G
Vrolix
Eric A
EA
Van Marck
Arnold G
AG
Herman
Paul A
PA
Pelckmans
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D004064:Digestive System / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D004386:Duodenum / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D007421:Intestine, Small / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D007537:Isometric Contraction / Q000502:physiology; D007583:Jejunum / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D012550:Schistosoma mansoni / Q000378:metabolism / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000473:pathology / Q000503:physiopathology*; D013004:Somatostatin / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D013779:Tetrodotoxin; D013004:Somatostatin; D001285:Atropine