Mesenteric afferent sensitivity to cholecystokinin and 5-hydroxytryptamine

The present electrophysiological investigation examines the effect of CCK a nd 5-hydroxytryptamine on gastrointestinal afferent fibre discharge. 5-HT m arkedly stimulated mesenteric afferents. The response was transient (<10s) and mediated by 5-HT3 receptors as demonstrated by the action of 2-methyl-5 -HT and antagonism by granisetron. CCK was also a potent stimulus to mesent eric afferents causing a long-lasting (>30s) increase in excitability. The response to CCK was mediated via the CCK, receptor as shown by the antagoni stic action of devazepide. At doses of granisetron and devazepide which com pletely block the response to exogenous 5-HT and CCK, the afferent fibres s till responded to both mechanical and chemical stimulation of the mucosa. T hus products of enteroendocrine cells can have profound effects on mucosal afferent sensitivity but do not play an obligatory role in afferent signal transduction. Key words: mesenteric afferent fibres, 5-HT, CCK.