The enteric nervous sytem and infectious diarrhoea. An experimental study in mouse and rat

Sammanfattning: Aim: To evaluate the role of the enteric nervous system in one of the most common types of infectious diarrhoea worldwide, rotavirus infection, and to further clarify the mechanisms behind neurally mediated intestinal secretion. Methods: The experiments were performed on neonatal and adult mice and adult rats. Experimental setups: In vitro: 1. Ussing chamber. 2. Perfusion chamber. In vivo: 1. Recording of secretion, measured as potential difference. 2. Assessment of clinical diarrhoea in an animal model. Results: Rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. Different drugs blocking nerve activity (tetrodotoxin, lidocaine and hexamethonium) were used to attenuate rotavirus-induced fluid and electrolyte secretion in vitro. Rotavirus diarrhoea was also reduced by neurotransmitter receptor antagonists against vasoactive intestinal peptide and serotonin-3 receptors. Both in vivo and in vitro data suggest that adult mice despite rotavirus replication do not get symptoms in terms of intestinal fluid secretion. Cholera secretion was partially inhibited by blockade of serotonin-3 receptors. Blockade of prostaglandin synthesis and vasoactive intestinal peptide receptors had an effect only if given together with the toxin, while blockade of nicotinic receptors had an effect only on manifest secretion. Cholera toxin simultaneously activated an inhibitory secretomotor mechanism via prostaglandins, serotonin-3 and muscarine receptors. Cholera toxin also induced a specific motor pattern, clusters, provided that the animals were pretreated with a blocker of prostaglandin synthesis, serotonin-3 or the muscarine receptor. Conclusions: This study confirms the importance of nervous mechanisms in secretory diarrhoea by demonstrating an important role in rotavirus disease. Cholera toxin seems to activate both excitatory and inhibitory systems simultaneously. Both the formation of clusters and the different effects of the drugs on developing and manifest secretion are compatible with uncontrolled firing in myenteric and submucous neuron networks. Blockade of uncontrolled network firing may be a new potential target in diarrhoeal disease.