The oxytocin/vasopressin receptor antagonist atosiban delays the gastric emptying of a semisolid meal compared to saline in human

BACKGROUND: Oxytocin is released in response to a meal. Further, mRNA for oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract. The aim of this study was therefore to examine whether oxytocin, or the receptor antagonist atosiban, influence the gastric emptying. METHODS: Ten healthy volunteers (five men) were examined regarding gastric emptying at three different occasions: once during oxytocin stimulation using a pharmacological dose; once during blockage of the oxytocin receptors (which also blocks the vasopressin receptors) and thereby inhibiting physiological doses of oxytocin; and once during saline infusion. Gastric emptying rate (GER) was assessed and expressed as the percentage reduction in antral cross-sectional area from 15 to 90 min after ingestion of rice pudding. The assessment was performed by real-time ultrasonography. At the same time, the feeling of satiety was registered using visual satiety scores. RESULTS: Inhibition of the binding of endogenous oxytocin by the receptor antagonist delayed the GER by 37 % compared to saline (p = 0.037). In contrast, infusion of oxytocin in a dosage of 40 mU/min did not affect the GER (p = 0.610). Satiation scores areas in healthy subjects after receiving atosiban or oxytocin did not show any significant differences. CONCLUSION: Oxytocin and/or vasopressin seem to be regulators of gastric emptying during physiological conditions, since the receptor antagonist atosiban delayed the GER. However, the actual pharmacological dose of oxytocin in this study had no effect. The effect of oxytocin and vasopressin on GI motility has to be further evaluated

The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department

Avpr1a variant associated with preschoolers' lower altruistic behavior

10.1371/journal.pone.0025274PLoS ONE69

Trans-Translation in Helicobacter pylori: Essentiality of Ribosome Rescue and Requirement of Protein Tagging for Stress Resistance and Competence

BACKGROUND: The ubiquitous bacterial trans-translation is one of the most studied quality control mechanisms. Trans-translation requires two specific factors, a small RNA SsrA (tmRNA) and a protein co-factor SmpB, to promote the release of ribosomes stalled on defective mRNAs and to add a specific tag sequence to aberrant polypeptides to direct them to degradation pathways. Helicobacter pylori is a pathogen persistently colonizing a hostile niche, the stomach of humans. PRINCIPAL FINDINGS: We investigated the role of trans-translation in this bacterium well fitted to resist stressful conditions and found that both smpB and ssrA were essential genes. Five mutant versions of ssrA were generated in H. pylori in order to investigate the function of trans-translation in this organism. Mutation of the resume codon that allows the switch of template of the ribosome required for its release was essential in vivo, however a mutant in which this codon was followed by stop codons interrupting the tag sequence was viable. Therefore one round of translation is sufficient to promote the rescue of stalled ribosomes. A mutant expressing a truncated SsrA tag was viable in H. pylori, but affected in competence and tolerance to both oxidative and antibiotic stresses. This demonstrates that control of protein degradation through trans-translation is by itself central in the management of stress conditions and of competence and supports a regulatory role of trans-translation-dependent protein tagging. In addition, the expression of smpB and ssrA was found to be induced upon acid exposure of H. pylori. CONCLUSIONS: We conclude to a central role of trans-translation in H. pylori both for ribosome rescue possibly due to more severe stalling and for protein degradation to recover from stress conditions frequently encountered in the gastric environment. Finally, the essential trans-translation machinery of H. pylori is an excellent specific target for the development of novel antibiotics

Linear V1-vascular vasopressin antagonists suitable for radioiodination, biotinylation, and fluorescent labeling

We modified several linear V1-vascular arginine vasopressin (AVP) antagonists to obtain compounds suitable for radioiodination, biotinylation, and fluorescent labeling. In binding competition experiments with human platelet V1-vascular AVP receptors, the linear V1 antagonist phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 (PhaaGln) displayed the greatest affinity [dissociation constant (Kd) = 0.05 +/- 0.01 nM]. The radioiodinated compound phenylacetyl-D-Tyr(Et)-Phe-Val-Asn-Lys-Pro-125I-labeled Tyr-NH2 (125I-labeled TyrPhaa) was characterized by a high affinity (Kd = 1.42 +/- 0.19 nM), a low nonspecific binding, and good stability. PhaaGln coupled to dodecabiotin retained a good affinity for V1-vascular AVP receptors (Kd = 1.41 +/- 0.20 nM). The complex PhaaGln-dodecabiotin-avidin is bifunctional, since an avidin-agarose column specifically bound V1-vascular AVP receptors labeled with 125I-TyrPhaa-dodecabiotin. In A7r5 vascular smooth muscle cells loaded with fura-2, PhaaGln and PhaaGln-dodecabiotin were pure antagonists as they blocked AVP-induced calcium mobilization but did not elicit a calcium signal by themselves. V1-vascular AVP receptors of A7r5 vascular smooth muscle cells were visualized by bound PhaaGln-dodecabiotin made fluorescent by labeling with fluorescein avidin. Thus linear V1-vascular AVP antagonists can be used as high affinity and specificity radioiodinated, biotinylated, and fluorescent probes to explore V1-vascular AVP receptors of human and animal origin