Effect of CCK pretreatment on the CCK sensitivity of rat polymodal gastric vagal afferent in vitro.
ABSTRACT 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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ABSTRACT: Ghrelin is a peptide predominantly produced by the stomach. Ghrelin displays strong GH-releasing activity. This activity is mediated by the activation of the so-called GH secretagogue receptor type 1a. This receptor had been shown to be specific for a family of synthetic, peptidyl and nonpeptidyl GH secretagogues. Apart from a potent GH-releasing action, ghrelin has other activities including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, and influence on pancreatic exocrine and endocrine function as well as on glucose metabolism. Cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system, are other actions of ghrelin. Therefore, we consider ghrelin a gastrointestinal peptide contributing to the regulation of diverse functions of the gut-brain axis. So, there is indeed a possibility that ghrelin analogs, acting as either agonists or antagonists, might have clinical impact.Endocrine Reviews 07/2004; 25(3):426-57. · 14.87 Impact Factor
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ABSTRACT: Nutrients in the intestine initiate changes in secretory and motor function of the gastrointestinal (GI) tract. The nature of the 'sensors' in the intestinal wall is not well characterized. Intestinal lipid stimulates the release of cholecystokinin (CCK) from mucosal entero-endocrine cells, and it is proposed that CCK activates CCK A receptors on vagal afferent nerve terminals. There is evidence that chylomicron components are involved in this lipid transduction pathway. The aim of the present study was to determine (1) the pathway mediating reflex inhibition of gastric motility and (2) activation of duodenal vagal afferents in response to chylomicrons. Mesenteric lymph was obtained from awake rats fitted with lymph fistulas during intestinal perfusion of lipid (Intralipid, 170 micromol h(-1), chylous lymph) or a dextrose and/or electrolyte solution (control lymph). Inhibition of gastric motility was measured manometrically in urethane-anaesthetized recipient rats in response to intra-arterial injection of lymph close to the upper GI tract. Chylous lymph was significantly more potent than control lymph in inhibiting gastric motility. Functional vagal deafferentation by perineural capsaicin or CCK A receptor antagonist (devazepide, 1 mg kg(-1), i.v.) significantly reduced chylous lymph-induced inhibition of gastric motility. The discharge of duodenal vagal afferent fibres was recorded from the dorsal abdominal vagus nerve in an in vitro preparation of the duodenum. Duodenal vagal afferent nerve fibre discharge was significantly increased by close-arterial injection of CCK (1-100 pmol) in 43 of 83 units tested. The discharge of 88% of CCK-responsive fibres was increased by close-arterial injection of chylous lymph; devazepide (100 microg, i.a.) abolished the afferent response to chylous lymph in 83% of these units. These data suggest that in the intestinal mucosa, chylomicrons or their products release endogenous CCK which activates CCK A receptors on vagal afferent nerve fibre terminals, which in turn initiate a vago-vagal reflex inhibition of gastric motor function.The Journal of Physiology 08/2003; 550(Pt 2):657-64. · 4.38 Impact Factor
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ABSTRACT: Noxious stimuli inhibit inflammation by activating neuroendocrine stress axes, an effect that is potently attenuated by ongoing activity in subdiaphragmatic vagal afferents. Because this vagal afferent activity is carried in the coeliac and coeliac accessory branches of the subdiaphragmatic vagus, we tested the hypothesis that the activity arises from vagal afferents that innervate a proximal segment of the gastrointestinal tract. Surgical removal of the duodenum, but not the stomach, produces a marked (six orders of magnitude) leftward shift in the dose-response curve for intraplantar capsaicin-induced inhibition of synovial plasma extravasation induced by the potent inflammatory mediator bradykinin, in the knee joint; this is similar in magnitude to the inhibition produced by subdiaphragmatic or by coeliac plus coeliac accessory branch vagotomy. Fasting, to unload mechanically sensitive polymodal afferents in the proximal gastrointestinal tract, produces a similar leftward shift in the dose-response curve for the inhibitory effect of capsaicin, an effect that is reversed by balloon distension in the duodenum in fasted rats, while balloon distension postvagotomy had no effect. These results suggest that activation of mechanically sensitive vagal afferents in the duodenum contributes vagal afferent activity that modulates neuroendocrine control of the inflammatory response.The Journal of Physiology 02/2004; 554(Pt 1):227-35. · 4.38 Impact Factor