Electrophysiological evidence for distinct vagal pathways mediating CCK‐evoked motor effects in the proximal versus distal stomach

• Published in: The Journal of physiology 2011-01, Vol.589 (2), p.371-393
• Main Authors: Okano‐Matsumoto, Shiho, McRoberts, James A., Taché, Yvette, Adelson, David W.
• Format: Article
• Language: English
• Subjects: Alimentary; Analysis of Variance; Animals; Dose-Response Relationship, Drug; Electrophysiology; Male; Neurons, Efferent - drug effects; Neurons, Efferent - physiology; Rats; Rats, Sprague-Dawley; Rodents; Sincalide - pharmacology; Stomach; Stomach - drug effects; Stomach - innervation; Stomach - physiology; Vagus Nerve - drug effects; Vagus Nerve - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2010.196832

Non‐technical summary Gut activity is controlled by the vagus nerves. In anaesthetized rats, both sensory and motor nerve activity evoked by intravenous injection of the gut hormone cholecystokinin were recorded in separate sub‐branches of the gastric vagus nerve that supply the forestomach and hindstomach, respectively. Activity in the forestomach branch has not been studied before. Motor nerve activity in response to cholecystokinin differed between the two branches, in both timing and direction. Motor output to the forestomach paralleled sensory input from the hindstomach, while motor output to the hindstomach paralleled sensory input from the intestines. The data suggest that cholecystokinin released in the intestines after a meal immediately influences churning and propulsion of food by the hindstomach, via reflexes initiated by nearby intestinal sensory nerve terminals, but may influence gastric capacity only later, once circulating levels of cholecystokinin rise to levels capable of activating sensors in the hindstomach.   Intravenous cholecystokinin octapeptide (CCK‐8) elicits vago‐vagal reflexes that inhibit phasic gastric contractions and reduce gastric tone in urethane‐anaesthetized rats. A discrete proximal subdivision of the ventral gastric vagus nerve (pVGV) innervates the proximal stomach, but the fibre populations within it have not been characterized previously. We hypothesized that i.v. CCK‐8 injection would excite inhibitory efferent outflow in the pVGV, in contrast to its inhibitory effect on excitatory efferent outflow in the distal subdivision (dVGV), which supplies the distal stomach. In each VGV subdivision, a dual‐recording technique was used to record afferent and efferent activity simultaneously, while also monitoring intragastric pressure (IGP). CCK‐8 dose dependently (100–1000 pmol kg−1, i.v.) reduced gastric tone, gastric contractile activity and multi‐unit dVGV efferent discharge, but increased pVGV efferent firing. Single‐unit analysis revealed a minority of efferent fibres in each branch whose response differed in direction from the bulk response. Unexpectedly, efferent excitation in the pVGV was significantly shorter lived and had a significantly shorter decay half‐time than did efferent inhibition in the dVGV, indicating that distinct pathways drive CCK‐evoked outflow to the proximal vs. the distal stomach. Efferent inhibition in the dVGV began several seconds before, and persisted significantly longer than, simultaneousl