Sensitivity of vagal mucosal afferents to cholecystokinin and its role in afferent signal transduction in the rat.

1. Extracellular recordings from rat mesenteric paravascular nerve bundles were made in order to characterize the responses of different populations of afferents supplying the small intestine to intravenous cholecystokinin (CCK; in the form of sulphated CCK8). 2. Approximately 70% of mesenteric nerve bundles contained CCK-sensitive afferent fibres. Responsive afferents had low spontaneous discharge (1.6 +/- 0.3 impulses s-1) and showed a 14-fold increase in firing at the peak of the response to 50 pmol CCK with the overall response lasting several minutes. The onset of the response occurred after a latency of (3.9 +/- 0.1 s) following i.v. administration of CCK, which corresponds largely to the circulation delay in these animals. The threshold dose of CCK was < 5 pmol. 3. The response to 100 pmol CCK was completely abolished by devazepide (0.5 mg kg-1) and by chronic subdiaphragmatic vagotomy performed 10-14 days prior to experimentation, indicating that CCK sensitivity was via CCKA receptors and exclusively mediated via vagal afferents rather than splanchnic or enteric afferents. 4. Evidence that CCK-sensitive afferents had mucosal receptive fields was indicated by the lack of any response to luminal distension and the sensitivity of the CCK response to luminal anaesthesia. Furthermore, CCK-sensitive afferents responded to luminal hydrochloric acid (50 mM) in a slowly adapting manner. The response to acid was significantly reduced (P < 0.005), but not abolished, by devazepide at a time when the response to exogenous CCK had been completely eliminated. 5. The exquisite sensitivity of some vagal mucosal afferents to CCK suggests that they may play a physiological role in the reflex and behavioural consequences of CCK release from the small intestine, possibly acting in a paracrine fashion. However, this sensitivity to CCK represents only one aspect of the broad chemosensitivity of these mucosal afferents and is not an obligatory component of the signal transduction pathway.