Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea

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Abstract
Background and aims: The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT3) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea. Methods: Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus. Results: While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04–3.56), the 5-HT3 receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe6,Leu17)-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31–2.9) (pConclusions: Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea; observations that could imply new principles for treatment of this disease with significant global impact.