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.
1 We examined the eects of adenosine receptor agonists and antagonists on the discharge of mesenteric aerent nerves supplying the jejunum in pentobarbitone sodium-anaesthetized rats. , i.v.) evoked increases in aerent nerve activity and intrajejunal pressure, hypotension and bradycardia. However, adenosine (3 mg kg 71 , i.v.) evoked greater increases in aerent nerve activity than bethanechol despite inducing smaller increases in intrajejunal pressure. 5 In summary, A 1 and A 2B and/or A 2B -like receptors evoke adenosine-induced increases in mesenteric aerent nerve activity and intrajejunal pressure in the anaesthetized rat. Furthermore, elevations in intrajejunal pressure do not wholly account for adenosine-evoked excitation of mesenteric aerent nerves.
The aim of the present study was to examine the sensitivity to opioid-receptor agonists of mesenteric afferents supplying the small intestine and to characterize the subpopulations of any responsive fibres. Mesenteric afferent discharge was recorded electrophysiologically in response to cumulative doses (1-400 microgram kg-1) of the mu-receptor agonist [D-ala,2 N- me-Phe4, Gly5-ol]-enkephalin (DAMGO), the delta-receptor agonist [D-ala,2 D-leu5]-enkephalin (DADLE) and the kappa-receptor agonist U-50488. DAMGO and DADLE, but not U-50488, markedly stimulated whole nerve mesenteric afferent discharge (P < 0.05) that was unrelated to intestinal motor events. Subpopulations of afferent fibres responding to DAMGO were examined using waveform analysis to identify single units from within the whole mesenteric nerve bundles. One population was CCK-sensitive (15/15 fibres) and the other was a subpopulation of mechanosensitive afferents that responded to distension (17/28). 5-HT-sensitive afferents did not respond to DAMGO (0/11). We conclude that specific subpopulations of mesenteric afferents respond to mu- and possibly delta- but not kappa-receptor agonists. This sensitivity to opioids may contribute to the antinociceptive property of vagal afferents.
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