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Best Practice & Research. Clinical... Dec 2016The present review initially describes the rationale for the use of non-adrenergic vasopressors in the treatment of distributive shock and then provides an overview of... (Review)
Review
The present review initially describes the rationale for the use of non-adrenergic vasopressors in the treatment of distributive shock and then provides an overview of the individual vasopressin-receptor agonists, namely arginine vasopressin, terlipressin, and selepressin. Following a brief summary of their current use in clinical practice, the present review focuses on the influence of vasopressin-receptor agonists on macro- and microvascular coupling, also referred to as hemodynamic coherence. On the basis of the current evidence from experimental and clinical studies, vasopressin-receptor agonists do not negatively influence macro- and microvascular coupling as compared to the standard therapy with norepinephrine, when used in established treatment regimes. A higher selectivity for the V-receptor seems to be beneficial; however, future clinical trials are warranted to verify this assumption. Notably, the optimal treatment regime for non-adrenergic vasopressors with respect to compound, dose, and timing still needs to be defined.
Topics: Adrenergic Agents; Hemodynamics; Humans; Microcirculation; Receptors, Vasopressin; Shock, Septic; Vasoconstrictor Agents
PubMed: 27931650
DOI: 10.1016/j.bpa.2016.10.010 -
Traffic (Copenhagen, Denmark) Jan 2018The signaling pathway of G protein-coupled receptors is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the...
The signaling pathway of G protein-coupled receptors is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the vasopressin receptor V subtype (V R) trafficking and its impact on receptor signaling and regulation. For this purpose, we investigated the role of β-arrestins in receptor desensitization, internalization and recycling and attempted to dissect the V R-mediated MAP kinase pathway. Using MEF cells Knocked-out for β-arrestins 1 and 2, we demonstrated that both β-arrestins 1 and 2 play a fundamental role in internalization and recycling of V R with a rapid and transient V R-β-arrestin interaction in contrast to a slow and long-lasting β-arrestin recruitment of the V vasopressin receptor subtype (V R). Using V R-V R chimeras and V R C-terminus truncations, we demonstrated the critical role of the V R C-terminus in its interaction with β-arrestins thereby regulating the receptor internalization and recycling kinetics in a phosphorylation-independent manner. In parallel, V R MAP kinase activation was dependent on arrestins and Src-kinase but independent on G proteins. Interestingly, Src interacted with hV R at basal state and dissociated when receptor internalization occurred. Altogether, our data describe for the first time the trafficking profile and MAP kinase pathway of V R involving both arrestins and Src kinase family.
Topics: Animals; Binding Sites; GTP-Binding Proteins; HEK293 Cells; Humans; MAP Kinase Signaling System; Mice; Protein Binding; Protein Transport; Receptors, Vasopressin; beta-Arrestins; src-Family Kinases
PubMed: 29044966
DOI: 10.1111/tra.12535 -
American Journal of Physiology. Renal... Mar 2021Renal arginine vasopressin receptor 2 (AVPR2) plays a crucial role in osmoregulation. Engagement of ligand with AVPR2 results in aquaporin 2 movement to the apical...
Renal arginine vasopressin receptor 2 (AVPR2) plays a crucial role in osmoregulation. Engagement of ligand with AVPR2 results in aquaporin 2 movement to the apical membrane and water reabsorption from the urinary filtrate. Despite this essential role, little is known about transcriptional regulation of . Here, we identify novel roles for PAX2, a transcription factor crucial for kidney development, and its adaptor protein, Pax transcription interacting protein (PTIP), for epigenetic regulation of and thus body water balance. Chromatin immunoprecipitation (ChIP) from murine inner medulla cells (IMCD-3) identified the minimal DNA-binding region of PAX2 on the promoter. Regulation of by PAX2 was confirmed using a heterologous DNA expression system. PAX2 recruits the adaptor protein PTIP and its associated histone methyltransferase (HMT) complex to promoter, imposing epigenetic marks on this region and throughout the coding sequence that modulate gene transcription. Reduction of PAX2 or PTIP protein levels by siRNA prevented histone lysine methylation and expression of . ChIP using mouse or human kidneys determined that PAX2 is highly enriched in the promoter alongside PTIP and HMT proteins, leading to high levels of histone H3 lysine trimethylation within the promoter and throughout the gene. In conclusion, PAX2 provides locus specificity for PTIP, allowing the HMT complex to impart epigenetic changes at the locus and regulate transcription. These finding have major implications for understanding regulation of body water balance. The transcription factor PAX2 plays an indispensable role in kidney development. In the adult kidney, we identified the first described protein this protein regulates. PAX2 and its interacting partner Pax transcription interacting protein recruit a histone methyltransferase complex to the promoter and epigentically regulate the expression of arginine vasopressin receptor 2, a protein that plays a crucial role in osmoregulation in the distal tubule.
Topics: Animals; Carrier Proteins; Cell Nucleus; Epigenesis, Genetic; Gene Expression Regulation; Nuclear Proteins; PAX2 Transcription Factor; Receptors, Vasopressin
PubMed: 33522413
DOI: 10.1152/ajprenal.00371.2020 -
American Journal of Physiology. Renal... Apr 2017The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic... (Review)
Review
The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis. In this brief review we assess the role of cyclic adenosine monophosphate (cAMP) and discuss the emerging concept that type 2 AVP receptor (V2R)-mediated AQP2 trafficking is cAMP-independent.
Topics: Animals; Aquaporin 2; Arginine Vasopressin; Body Water; Cell Membrane; Cyclic AMP; Epithelial Cells; Humans; Kidney Tubules, Collecting; Protein Transport; Receptors, Vasopressin; Second Messenger Systems; Water-Electrolyte Balance
PubMed: 28179252
DOI: 10.1152/ajprenal.00010.2017 -
World Journal of Gastroenterology Nov 2015Hyponatremia is a frequent complication of advanced cirrhosis with ascites associated with increased morbidity and mortality. It is caused by an impairment in the renal... (Review)
Review
Hyponatremia is a frequent complication of advanced cirrhosis with ascites associated with increased morbidity and mortality. It is caused by an impairment in the renal capacity to eliminate solute-free water and is considered to be related to persistent secretion of vasopressin despite low serum osmolality. This nonosmotic release of vasopressin is mediated by the autonomic nervous system, which senses the underfilling of arterial vascular component. This reduction of effective arterial blood volume is closely related to the development of ascites. Although the short-time effects of vasopressin V2 receptor antagonists (vaptans) on hyponatremia and ascites have been repeatedly reported, their effects on the long-term management of cirrhotic ascites have not been established yet. Considering that their effects on water diuresis and their safety are limited by severe underfilling state of patients, cautious approaches with adequate monitoring are needed to advanced cirrhosis. Proper indication, adequate doses and new possibility of combination therapy should be explored in the future controlled study. As hyponatremia is frequent obstacle to ascites management, judicious combination with low-dose diuretics may decrease the incidence of refractory ascites. Although vaptans show much promise in the treatment of advanced cirrhosis, the problem of high cost should be solved for the future.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Ascites; Biomarkers; Humans; Liver Cirrhosis; Neurophysins; Patient Selection; Protein Precursors; Receptors, Vasopressin; Risk Factors; Treatment Outcome; Vasopressins; Water-Electrolyte Balance
PubMed: 26556988
DOI: 10.3748/wjg.v21.i41.11584 -
Acta Medica Indonesiana Jul 2022This is a literature review of the use of aquaretic in patients with acute decompensated heart failure (ADHF), including the physiologic function of vasopressin and its... (Review)
Review
This is a literature review of the use of aquaretic in patients with acute decompensated heart failure (ADHF), including the physiologic function of vasopressin and its mechanism of action in heart failure patients, and aquaretic drugs with their respective risks and benefits.Vasopressin is one of several hormones that can cause hyponatremia and worsen congestion in ADHF patients. Aquaretics are a class of drugs that have an antagonistic effect on vasopressin receptors, especially V2R. Aquaretics use in ADHF patients can provide relief for congestive symptoms with no serious adverse effects. In-depth additional understanding regarding aquaretics may be useful for clinical judgments in treating ADHF patients.
Topics: Acute Disease; Heart Failure; Humans; Receptors, Vasopressin; Vasopressins
PubMed: 36156485
DOI: No ID Found -
Cancer Chemotherapy and Pharmacology Oct 2017Small-molecule inhibitors of heat-shock protein 90 (HSP90) have been under development as chemotherapeutic agents. The adverse events reported from early clinical trials...
PURPOSE
Small-molecule inhibitors of heat-shock protein 90 (HSP90) have been under development as chemotherapeutic agents. The adverse events reported from early clinical trials included hyponatremia. Given the limited number of patients enrolled, the number of hyponatremia incidents was remarkable and repeatedly, the event was judged as severe. Inappropriate V2 vasopressin receptor stimulation is an established cause of hyponatremia. We explored the hypothesis that HSP90 inhibition produces hypersensitivity to vasopressin by upregulating V2-receptors.
METHODS
Experiments were carried out in cell culture using HEK293 cells with heterologous expression of the human V2-receptor and HELA cells with an endogenous V2-receptor complement. We tested the effect of HSP90 inhibition by three structurally unrelated compounds (alvespimycin, luminespib, radicicol) and asserted its specificity in cells depleted of cytosolic HSP90 (by RNA interference). Assays encompassed surface V2-receptor density and vasopressin-stimulated formation of cyclic AMP (cAMP).
RESULTS
The results demonstrate a twofold increase in cell-surface receptor density following pre-incubation with each of the HSP90 inhibitors. The effect had a concentration-dependence consistent with the individual potencies to inhibit HSP90. Similarly, depletion of cytosolic HSP90 increased surface-receptor density and at the same time, reduced the inhibitor effect. Upregulated V2-receptors were fully functional; hence, in culture treated with an HSP90 inhibitor, addition of vasopressin resulted in higher levels of cAMP than in controls.
CONCLUSION
Since formation of cAMP is the first signalling step in raising water permeability of the collecting duct epithelia, we suggest that V2-receptor upregulation generates hypersensitivity to vasopressin linking HSP90 inhibition to the development of hyponatremia.
Topics: Benzoquinones; Cyclic AMP; Cytosol; HEK293 Cells; HSP90 Heat-Shock Proteins; HeLa Cells; Humans; Hyponatremia; Isoxazoles; Lactams, Macrocyclic; Macrolides; RNA Interference; Receptors, Vasopressin; Resorcinols; Up-Regulation; Vasopressins
PubMed: 28779264
DOI: 10.1007/s00280-017-3390-x -
Peptides Jul 2024Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus... (Review)
Review
Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus (SCN), the center of the circadian clock in mammals, is composed of multiple cell types that form a network that provides the basis for the remarkable stability of the circadian clock. Among the neuropeptides expressed in the SCN, arginine vasopressin (AVP) has attracted much attention because of its deep involvement in the function of circadian rhythms, as elucidated in particular by studies using genetically engineered mice. This review briefly summarizes the current knowledge on the peptidergic distribution and topographic neuronal organization in the SCN, the molecular mechanisms of the clock genes, and the relationship between the SCN and peripheral clocks. With respect to the physiological roles of AVP and AVP-expressing neurons, in addition to a sex-dependent action of AVP in the SCN, studies using AVP receptor knockout mice and mice genetically manipulated to alter the clock properties of AVP neurons are summarized here, highlighting its importance in maintaining circadian homeostasis and its potential as a target for therapeutic interventions.
Topics: Animals; Arginine Vasopressin; Suprachiasmatic Nucleus; Homeostasis; Circadian Rhythm; Humans; Mice; Circadian Clocks; Neurons; Mice, Knockout; Receptors, Vasopressin
PubMed: 38663583
DOI: 10.1016/j.peptides.2024.171229 -
Life Science Alliance Aug 2024It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs)...
It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs) heteromerize with α-adrenoceptors (α-ARs) through which CRs are regulated. Here, we show that arginine vasopressin receptor 1A (AVPR1A) heteromerizes with all human CRs, except chemokine (C-X-C motif) receptor (CXCR)1, in recombinant systems and that such heteromers are detectable in THP-1 cells and human monocytes. We demonstrate that ligand-free AVPR1A differentially regulates the efficacy of CR partners to mediate chemotaxis and that AVPR1A ligands disrupt AVPR1A:CR heteromers, which enhances chemokine (C-C motif) receptor (CCR)1-mediated chemotaxis and inhibits CCR2-, CCR8-, and CXCR4-mediated chemotaxis. Using bioluminescence resonance energy transfer to monitor G protein activation and CRISPR/Cas9 gene-edited THP-1 cells lacking AVPR1A or α-AR, we show that CRs that share the propensity to heteromerize with α-ARs and AVPR1A exist and function within interdependent hetero-oligomeric complexes through which the efficacy of CRs to mediate chemotaxis is controlled. Our findings suggest that hetero-oligomers composed of CRs, α-ARs, and AVPR1A may enable stress hormones to regulate immune cell trafficking.
Topics: Humans; Monocytes; Chemotaxis; Receptors, Chemokine; Receptors, Vasopressin; THP-1 Cells; Protein Multimerization; HEK293 Cells; Receptors, CXCR4; CRISPR-Cas Systems; Signal Transduction; Receptors, Adrenergic, alpha-1; Ligands
PubMed: 38782603
DOI: 10.26508/lsa.202402657 -
International Journal of Molecular... Aug 2021Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its... (Review)
Review
Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its effect is well characterized through V2 receptors, which regulates the water resorption in kidney, while its vasoconstrictory effect through V1a receptor also received a lot of attention in the maintenance of blood pressure during shock. However, the most striking is its central effect both through the V1b receptors in stress-axis regulation as well as through V1a receptors regulating many aspects of our behavior (e.g., social behavior, learning and memory). Vasopressin has been implicated in the development of depression, due to its connection with chronic stress, as well as schizophrenia because of its involvement in social interactions and memory processes. Epigenetic changes may also play a role in the development of these disorders. The possible mechanism includes DNA methylation, histone modification and/or micro RNAs, and these possible regulations will be in the focus of our present review.
Topics: Animals; Epigenesis, Genetic; Homeostasis; Humans; Mental Disorders; Receptors, Vasopressin; Signal Transduction; Vasopressins
PubMed: 34502322
DOI: 10.3390/ijms22179415