Effect of CCK pretreatment on the CCK sensitivity of rat polymodal gastric vagal afferent in vitro

Digestive Diseases Division, Department of Medicine, Center for Ulcer Research and Education/Digestive Diseases Research Center and Brain Research Institute, University of California Los Angeles School of Medicine, 90095, USA.
AJP Endocrinology and Metabolism (Impact Factor: 3.79). 10/2000; 279(3):E695-706.
Source: PubMed


To prevent the blood-borne interference and reflex actions via neighboring organs and the central nervous system, the study was conducted in an in vitro isolated stomach-gastric vagus nerve preparation obtained from overnight-fasted, urethan-anesthetized rats. Afferent unit action potentials were recorded from the gastric branch of the vagus nerve. The left gastric artery was catheterized for intra-arterial injection. In vitro we found that 1) 55/70 gastric vagal afferents (GVAs) were polymodal, responding to CCK-8 and mechanical stimuli, 13 were mechanoreceptive, and 2 were CCK-responsive; 2) sequential or randomized intra-arterial injections of CCK-8 (0.1-200 pmol) dose-dependently increased firing rate and reached the peak rate at 100 pmol; 3) the action was suppressed by CCK-A (Devazepide) but not by CCK-B (L-365,260) receptor antagonist; 4) neither antagonist blocked the mechanosensitivity of GVA fibers. These results are consistent with corresponding in vivo well-documented findings. Histological data indicate that the layered structure of the stomach wall was preserved in vitro for 6-8 h. Based on these results, it seems reasonable to use the in vitro preparation for conducting a study that is usually difficult to be performed in vivo. For instance, because there was no blood supply in vitro, the composition of the interstitial fluid, i.e., the ambient nerve terminals, can be better controlled and influenced by intra-arterial injection of a defined solution. Here we report that acutely changing the ambient CCK level by a conditioning stimulus (a preceding intra-arterial injection of increasing doses of CCK-8) reduced the CCK sensitivity of GVA terminals to a subsequent test stimulus (a constant dose of CCK-8 intra-arterial injection).

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    • "In this study we have identified both a visceral organ, the duodenum, from which vagal afferent activity arises to potently modulate noxious stimulus-induced inhibition of bradykinin plasma extravasation, as well as a specific physiological stimulus, mechanical stimulation, which modulates the inflammatory response by activity in subdiaphragmatic vagal afferents. While it is not known whether other stimuli, alone or by interacting with mechanical stimuli, also contribute to this effect of vagal afferent activity on inflammation, it seems likely since most duodenal vagal afferents are polymodal, responding to nutrients, osmotic stimuli and inflammatory mediators, as well as to mechanical stimuli; in fact, some are silent to mechanical stimuli until exposed to inflammatory mediators (Cottrell & Iggo, 1984; Grundy, 1988; Grundy & Scratchard, 1989; Berthoud et al. 1992; Wei & Wang, 2000; Zhu et al. 2001). Our observed effects of a 48 h fast could be due to changes independent of physical removal of luminal contents (e.g. "
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