title: Electrophysiological evidence for distinct vagal pathways mediating CCK-evoked motor effects in the proximal versus distal stomach.
abstract: 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, simultaneously recorded dVGV afferent excitation.Thus, dVGV afferent excitation could not account for the pattern of dVGV efferent inhibition. However, the time course of dVGV afferent excitation paralleled that of pVGV efferent excitation. Similarly, the duration of CCK-8-evoked afferent responses recorded in the accessory celiac branch of the vagus (ACV) matched the duration of dVGV efferent responses. The observed temporal relationships suggest that postprandial effects on gastric complicance of CCK released from intestinal endocrine cells may require circulating concentrations to rise to levels capable of exciting distal gastric afferent fibres, in contrast to more immediate effects on distal gastric contractile activity mediated via vago-vagal reflexes initiated by paracrine excitation of intestinal afferents.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd, Osaka, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Okano-Matsumoto
authors.forename: James A
authors.initials: JA
authors.lastname: McRoberts
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
authors.forename: David W
authors.initials: DW
authors.lastname: Adelson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008297:Male; D009476:Neurons, Efferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D012844:Sincalide