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Background Nowadays, chemotherapy induced nausea and vomiting ( CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 ( NK1) receptor and antagonists of NK1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus ( DMNV), on the cisplatin-induced emesis in rats and the possible mechanism. Methods Rats' kaolin intake, food intake, and bodyweight were recorded every day; gastric contraction activity was recorded in conscious rats through a force transducer implanted into the stomach; gastric emptying was monitored using the phenol red method; single unit extracellular firing in the DMNV were recorded. Key Results DMNV microinjection of CP-99 994 reduced the changes of increased kaolin consumption and suppressed food intake in cisplatin-treated rats; enhanced the gastric contraction activity dose-dependently in control and cisplatin-treated rats but enhanced gastric emptying only in cisplatin-treated rats; reduced the firing rate of gastric distention inhibited ( GD-I) neurons but increased the firing rate of GD excited ( GD-E) neurons in the DMNV. The effects of CP-99 994 on gastric motility and neuronal activity were stronger in cisplatin-treated rats than those of control rats. Conclusions and Inferences Our results suggested that CP-99 994 could improve emesis induced by cisplatin by regulating gastric motility and gastric related neuronal activity in the DMNV. [ABSTRACT FROM AUTHOR]

Background Gastric electrical stimulation ( GES) is implicated as a potential therapy for difficult-to-treat nausea and vomiting; however, there is a lack of insight into the mechanisms responsible for these effects. This study tested the relationship between acute GES and emesis in musk shrews, an established emetic model system. Methods Urethane-anesthetized shrews were used to record emetic responses (monitoring intra-tracheal pressure and esophageal contractions), respiration rate, heart rate variability, blood pressure, and gastrointestinal electromyograms. We investigated the effects of acute GES pulse duration (0.3, 1, 5, and 10 ms), current amplitude (0.5, 1, and 2 mA), pulse frequency (8, 15, 30, and 60 Hz), and electrode placement (antrum, body, and fundus) on emesis induced by gastric stretch, using a balloon. Key Results There were four outcomes: (i) GES did not modify the effects of gastric stretch-induced emesis; (ii) GES produced emesis, depending on the stimulation parameters, but was less effective than gastric stretch; (iii) other physiological changes were closely associated with emesis and could be related to a sub-threshold activation of the emetic system, including suppression of breathing and rise in blood pressure; and (iv) a control experiment showed that 8- OH- DPAT, a reported 5- HT1A receptor agonist that acts centrally as an antiemetic, blocked gastric stretch-induced emesis. Conclusions and Inferences These results do not support an antiemetic effect of acute GES on gastric distension-induced emesis within the range of conditions tested, but further evaluation should focus on a broader range of emetic stimuli and GES stimulation parameters. [ABSTRACT FROM AUTHOR]

Background The aims of this study were to investigate the effect of gastric electrical stimulation ( GES) with different parameters on emesis induced by apomorphine, and possible center mechanisms by brain functional magnetic resonance imaging (f MRI). Methods Six dogs implanted with electrodes on gastric serosa were used in this study. Part 1: Apomorphine was injected in the control session and GES sessions. GESs with different parameters were applied in GES session. Gastric slow waves and emesis and behaviors suggestive of nausea were recorded in each session. Part 2: Each dog was anesthetized and given GESs with different parameters or sham stimulation for 15 min after baseline (5 min), respectively. The location of cerebral activation induced by GES was investigated by f MRI. Key Results Apomorphine induced emesis and behaviors suggestive of nausea, and gastric dysrhythmia. The emesis frequency in control session was 5.5 ± 0.99, and symptoms score was 22.17 ± 1.01. GES with short pulse and long pulse could not improve emesis and symptoms induced by apomorphine. The emesis frequency (4.5 ± 0.76 in short pulse and 6.33 ± 1.05 in long pulse) and symptoms scores had no significant difference compared to control session (each p > 0.05). GES with trains of short pulse reduced emesis time frequency (3.83 ± 0.7, p = 0.042 vs control) and symptoms score ( p = 0.037 vs control) obviously. Brain f MRI showed that GES with short pulse and long pulse activated brain stem region, and trains of short pulse made amygdala and occipital lobe activation. Conclusions & Inferences Apomorphine induced emesis and gastric dysrhythmia. GES with trains of short pulses relieves emetic responses through activation of amygdala region. [ABSTRACT FROM AUTHOR]

Background Impaired 5- HT3 receptor function is likely involved in the pathogenesis of functional gastrointestinal disorders ( FGID) and 5- HT3 receptor antagonists are effective treatments for chemotherapy-induced nausea and vomiting ( CINV) and irritable bowel syndrome ( IBS). The monoterpene alcohol menthol and the aporphine alkaloid boldine combat symptoms of gastrointestinal diseases; both interact with other members of the Cys-loop ligand-gated ion channel family and may therefore also act on 5- HT3 receptors. Methods The impact of boldine and menthol on human recombinant homomeric 5- HT3A- and heteromeric 5- HT3 AB receptors in HEK293 cells was determined by radioligand binding, a luminescence-based Ca2+ assay, and a membrane potential assay. 5- HT3 protein and m RNA expression was assessed in human colon tissue. Key Results Boldine and menthol inhibited the 5- HT-induced activation of 5- HT3 receptors in the low and middle micromolar range, respectively. Boldine was a competitive antagonist of both receptors being 6.5- to 10-fold more potent at 5- HT3A- vs 5- HT3 AB receptors. Menthol non-competitively and stereoselectively inhibited both receptors: In contrast to (+)-menthol, (−)-menthol was significantly more potent toward 5- HT3A- vs 5- HT3 AB receptors. We show co-expression of 5- HT3A and 5- HT3B subunits in the human gut epithelium, the lamina propria, the myenteric plexus, and the muscular cell layer. Conclusions & Inferences The demonstrated 5- HT3 inhibitory effects may be relevant for boldine's and menthol's alleviating properties on FGID and may encourage clinical studies with the compounds or the plant extracts for CINV and IBS treatment. The found receptor-discriminative properties make boldine and (−)-menthol to potentially useful tools for analyzing structural differences between these receptor subtypes. [ABSTRACT FROM AUTHOR]