Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.5 (urease)
 7,257 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspeptic patients with or without Helicobacter pylori infection, and to determine the 5-HT receptor subtypes functionally involved. Biopsies from the second part of duodenum were obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were mounted in modified Ussing chambers with air suction for measurements of short-circuit current by a previously validated technique. Short-circuit current was measured before and after application of graded cumulative doses of 5-HT and a single dose of bumetanide (an inhibitor of chloride/bicarbonate transport), or one of the selective 5-HT receptor antagonists: ketanserin, ondansetron, or SB-204070 (1-butyl-4 piperidinmethyl-8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-carboxylate HCl). Histological examination was performed on duodenal biopsies. Helicobacter urease testing and histological examination determined Helicobacter pylori infection. 5-HT induced a dose-dependent and bumetanide-sensitive short-circuit current, which was independent of the presence of Helicobacter pylori infection. All the three 5-HT receptor antagonists failed to significantly effect basal and 5-HT-induced short-circuit current. Our results indicate that in human duodenum 1) 5-HT is a potent stimulator of bumetanide-sensitive secretion, 2) the serotonergic receptor subtype, which acts as the main mediator of 5-HT-induced secretion is different from the 5-HT(2), 5-HT(3), and the 5-HT(4) subtype and, 3) the sensitivity to 5-HT is not altered by Helicobacter pylori infection.
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PMID:Functional characterization of serotonin receptor subtypes in human duodenal secretion. 1644 86

The use of naturally occurring plant-derived compounds for controlling insect pests remains an attractive alternative to potentially dangerous synthetic chemical compounds. One prospective plant-based compound, isoforms of the so-called jack bean urease (JBU) from the jack bean, Canavalia ensiformis, as well a derived peptide, Jaburetox-2Ec, have insecticidal effects on an array of insect species. In the Chagas' disease vector, Rhodnius prolixus, some of the physiological effects attributed to these urease isoforms include inhibition of serotonin (5-HT)-stimulated fluid secretion by the Malpighian tubules (MTs). Here, we investigated whether the effects of these exogenous urease isoforms were targeting the neuroendocrine network involved in the anti-diuretic hormone (RhoprCAPA-2) signaling cascade. We show that pharmacological agents known to interfere with eicosanoid metabolite biosynthesis do not affect RhoprCAPA-2 inhibition of 5-HT-stimulated fluid secretion by MTs. In addition, we demonstrate that RhoprCAPA-2 inhibition of MTs is independent of extracellular or intracellular calcium. Using a heterologous system for analysis of receptor activation, we show that neither JBU nor Jaburetox-2Ec are agonists of the anti-diuretic hormone receptor, RhoprCAPAr1. Finally, activation of the receptor using sub-maximal doses of the natural ligand, RhoprCAPA-2, was not influenced by the presence of either JBU or Jaburetox-2Ec indicating that the urease isoforms do not compete with RhoprCAPA-2 for binding and activation of RhoprCAPAr1. Taken together, these results suggest that at least two distinct mechanisms leading to inhibition of fluid secretion by MTs exist in R. prolixus and, unlike the urease-related effects, the eicosanoid metabolite pathway is not involved in RhoprCAPA-2 mediated anti-diuresis.
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PMID:Investigation of the potential involvement of eicosanoid metabolites in anti-diuretic hormone signaling in Rhodnius prolixus. 2207 22

Previously we reported that gene expression of astrocytic 5-HT2B receptors was decreased in brains of depressed animals exposed to chronic mild stress (CMS) (Li et al., 2012) and of Parkinson's disease (Song et al., 2018). Depression is also one of the psychiatric symptoms in hyperammonemia, and astrocyte is a primary target of ammonium in brain in vivo. In the present study, we have used preparations of the brains of urease-treated mice and ammonium-treated astrocytes in culture to study gene expression and function of 5-HT2B receptors. The urease-treated mice showed depressive behaviour. Both mRNA and protein of 5-HT2B receptors were increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. Further study revealed that mRNA and protein expression of adenosine deaminase acting on RNA 2 (ADAR2), an enzyme catalyze RNA deamination of adenosine to inosine was increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. This increase in ADAR2 induced RNA editing of 5-HT2B receptors. Cultured astrocytes treated with ammonium lost 5-HT induced Ca2+ signalling and ERK1/2 phosphorylation, indicating dysfunction of 5-HT2B receptors. This is in agreement with our previous observation that edited 5-HT2B receptors no longer respond to 5-HT (Hertz et al., 2014). Ammonium effects are inhibited by ADAR2 siRNA in cultured astrocytes, suggesting that increased gene expression and editing and loss of function of 5-HT2B receptors are results of increased activity of ADAR2. In summary, we have demonstrated that functional malfunction of astrocytic 5-HT2B receptors occurs in animal models of major depression, Parkinson depression and hepatic encephalopathy albeit via different mechanisms. Understanding the role of astrocytic 5-HT2B receptors in different pathological contexts may instigate development of novel therapeutic strategies for treating disease-specific depressive behaviour.
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PMID:Ammonium induced dysfunction of 5-HT2B receptor in astrocytes. 3114 70