An electrophysiological investigation of the effects of cholecystokinin on enteric neurons

Cholecystokinin (CCK) is a peptide, which is present in the gastrointestinat tract in endocrine cells and in the enteric nervous system (ENS). A possible function in the control of motility of the small intestine has been attributed to neuronal CCK. The aim of this thesis was to obtain a fundamental insight into the action and effects of CCK on enteric neurons. Therefore, intracelluiar recordings were made of myenteric neurons in an isolated preparation of the guinea-pig ileum. Two types of excitable myenteric neurons were distinguished. Neurons in which the action potential showed a pronounced inflexion (shoulder) on the falling phase, were classified as AH neurons, the others as S neurons. The effects of CCK-8 and CCK-8NS on both types of neurons were determined. Application of CCK evoked dissimilar excitatory effects in the two types of neurons, which presumably are related to the function of these neurons in the ENS. Application of CCK evoked excitatory effects on almost all S neurons (inter- or motor-neurons). The effect was mediated by both CCK A and CCK B receptor subtypes and was different for both receptor subtypes with respect to action in time. Some S neurons possessed exclusively the CCK, or the CCK, receptor subtype, but others possessed both subtypes. The predominant effect of CCK on AH neurons (sensory neurons) was also slow excitation. These AH neurons were all endowed with both CCK receptor subtypes. The CCK A and CCK B , receptor subtypes on AH neurons had not only a different affinity for CCK, but also mediated the effects through different ionic channels. Results of experiments in which the effects of CCK antagonists on synaptic transmission were determined, showed that CCK in the ENS has besides a hormonal function, a function as neurotransmitter.