Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a non-peptide compound, HSP-117, antagonist of the tachykinin NK-1 receptor. Binding of 3H-substance P (SP) to the membranes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,994, the inhibitory activity of HSP-117 being about 50-fold that of CP-99,994. The SP-induced firing responses of single neuron activity in slices of the nucleus tractus solitarius of ferrets were inhibited by 10 microM HSP-117. Intracerebroventricular injection of HSP-117 significantly inhibited retching and vomiting induced by copper sulphate and morphine and the inhibitory effect of HSP-117 on emesis was greater than that of CP-99,994. These results indicate that (1) HSP-117 is a potent anti-emetic agent, blocking NK-1 receptors in the nucleus tractus solitarius and (2) NK-1 receptors in the nucleus tractus solitarius play an important role in emesis induced by broad-spectrum emetic stimuli.
 ...
PMID:Anti-emetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets. 1021 84

Substance P (SP) is a member of the tachykinin family of bioactive peptides and has highest affinity for the NK-1 receptor. We have developed the non-peptide compound HSP-117 as a selective antagonist of the NK-1 receptor. Binding of 3H-SP to the membranes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,994, the inhibitory activity of HSP-117 being 50-fold that of CP-99,994. The SP-induced firing responses of single neuron activity in slices of the nucleus tractus solitarius of ferrets were inhibited by 10 microM HSP-117. Intracerebroventricular injection of HSP-117 significantly inhibited retching and vomiting induced by copper sulphate and morphine and the inhibitory effect of HSP-117 on emesis was greater than that of CP-99,994. Moreover, emesis induced by copper sulphate and morphine were inhibited by the microinjection of HSP-117 and CP-99,994 into the area postrema and by lesion of the area postrema. These results indicate that HSP-117 is a potent anti-emetic agent, blocking NK-1 receptors in the area postrema and that NK-1 receptors in the area postrema play an important role in emesis induced by broad-spectrum emetic stimuli.
 ...
PMID:[The role of tachykinin NK-1 receptors in emetic action in the area postrema of ferrets]. 1062 82

The role of tachykinin NK-1 receptors in the area postrema (AP) in emesis was examined in ferrets. Strong c-fos-like immunoreactivity was observed in the AP and nucleus tractus solitalius (NTS) in cisplatin (10 mg/kg, i.p.)-treated animals, but not in control animals. The number of the central emetogen morphine-induced vomits and retches was remarkably reduced (95%) and that of the peripheral emetogen copper sulphate-induced vomits was significantly (54%) reduced by AP lesion. Pretreatment with the tachykinin NK-1 receptor antagonists HSP-117 (1.0 microg) and CP-99,994 (7.5 microg) into the AP decreased the numbers of vomits and retches induced by morphine and copper sulphate. These results suggest that NK-1 receptors in the AP are involved in the mechanism of emesis induced by morphine and copper sulphate.
 ...
PMID:The role of tachykinin NK-1 receptors in the area postrema of ferrets in emesis. 1082 52

The effects of a novel tachykinin NK1-receptor antagonist HSP-117 [(2S,3S)-3-[(5-isopropyl-2,3-dihydrobenzofuran-7-yl)methyl]amino-2-phenylpiperidine dihydrochloride] on cisplatin-induced pica, i.e., the eating of nonnutritive substances such as kaolin were examined in rats. HSP-117 inhibited kaolin intake in a dose-dependent manner for 2 days. The 5-HT3-receptor antagonist ondansetron inhibited only on the first day, but not on the second day. These results indicate that the cisplatin-induced kaolin intake on the first day is related to both 5-HT3- and NK1 receptors, while only the NK1 receptor is involved on the second day. Thus, cisplatin-induced continuous pica in rats represents a useful model of not only acute but also delayed emesis.
 ...
PMID:Effects of HSP-117, a novel tachykinin NK1-receptor antagonist, on cisplatin-induced pica as a new evaluation of delayed emesis in rats. 1148 39

Helicobacter pylori proteins CagA (cytotoxin-associated gene A) and VacA (vacuolating cytotoxin A) are among the virulence factors of this species. CagA gene carrying H. pylori strains are particularly associated with gastric adenocarsinoma. This study was conducted to evaluate Western Blot (WB) method to determine specific H. pylori antibodies in a group of patients with gastric cancer and in a control group with no malignancy. A total of 99 patients with gastric cancer (94 adenocarcinoma, 2 adenosquamous cell carcinoma, 3 non-Hodgkin lymphoma) and 150 control cases with epigastric complaints such as nausea, vomiting, diarrhea, gastroesophageal reflux and abdominal pain, were included to the study. H. pylori IgG-ELISA was positive in all study (mean age: 56.7 +/- 1.2 years, 62 male) and control (mean age: 24.2 +/- 1.3 years, 64 male) patients. Specific antibodies against CagA, VacA, OMP (outer membrane protein)-67, urease-A, urease-B, HSP (heat shock protein) and flagellin antigens determined by a commercial WB-based kit (RIDA Blot Helicobacter, R-Biopharm GmbH, Germany). Interestingly, no anti-VacA positivity was detected in none of the patient and control groups. The positivity rates for H. pylori CagA, OMP-67, urease A, urease-B, flagellin and HSP specific antibodies were as 78%, 54%, 37%, 60%, 53% and 82% in the gastric cancer group and 85%, 71%, 55%, 43%, 61% and 75% in the control group, respectively. There was no statistically significant difference (p > 0.05) between gastric carcinoma and control groups in terms of CagA, HSP and flagellin antibodies (p > 0.05). On the other hand, a statistically significant difference was found between the 2 groups in terms of urease-A, urease-B and OMP-67 (p < 0.01). These results suggested that this test should be assessed again by the manufacturer for its detection power directed towards specific H. pylori antibodies, especially for Vac-A. Further molecular and clinical studies are necessary to determine the factors that affect H. pylori virulence and disease prognosis.
 ...
PMID:[Evaluation of Western Blot method for the detection of antibodies to Helicobacter pylori antigens in patients with gastric carcinoma and cases with epigastric complaints]. 2045 95