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 bun dles were made in order to characterize the responses of different pop ulations of afferents supplying the small intestine to intravenous cho lecystokinin (CCK; in the form of sulphated CCK8). 2. Approximately 70 % of mesenteric nerve bundles contained CCX-sensitive afferent fibres. Responsive afferents had low spontaneous discharge (1.6 +/- 0.3 impul ses 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 minu tes. The onset of the response occurred after a latency of (3.9 +/- 0. 1 s) following I.V. administration of CCK, which corresponds largely t o the circulation delay in these animals. The threshold dose of CCK wa s < 5 pmol. 3. The response to 100 pmol CCK was completely abolished b y devazepide (0.5 mg kg(-1)) and by chronic subdiaphragmatic vagotomy performed 10-14 days prior to experimentation, indicating that CCK sen sitivity was via CCKA receptors and exclusively mediated via vagal aff erents rather than splanchnic or enteric afferents. 4. Evidence that C CK-sensitive afferents had mucosal receptive fields was indicated by t he lack of any response to luminal distension and the sensitivity of t he CCK response to luminal anaesthesia. Furthermore, CCK-sensitive aff erents responded to luminal hydrochloric acid (50 mns) in a slowly ada pting manner. The response to acid was significantly reduced (P < 0.00 5), but not abolished, by devazepide at a time when the response to ex ogenous CCK had been completely eliminated. 5. The exquisite sensitivi ty 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 fash ion. However, this sensitivity to CCK represents only one aspect of th e broad chemosensitivity of these mucosal afferents and is not an obli gatory component of the signal transduction pathway.