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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 -
The Journal of Headache and Pain Dec 2022Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an...
BACKGROUND
Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology. CGRP signaling could be a target of hormones that influence migraine. Our aim is to identify the expression of vasopressin and its receptors in the brain and in the trigeminovascular system with focus on the migraine-related regions and, furthermore, to examine the role of sex on the expression of neurohormones in the trigeminal ganglion.
METHODS
Rat brain and trigeminal ganglia were carefully harvested, and protein and mRNA levels were analyzed by immunohistochemistry and real-time PCR, respectively.
RESULTS
Vasopressin and its receptors immunoreactivity were found in migraine-related areas within the brain and, in the trigeminal ganglion, predominantly in neuronal cytoplasm. There were no differences in the number of positive immunoreactivity cells expression of CGRP and vasopressin in the trigeminal ganglion between male and female rats. In contrast, the number of RAMP1 (CGRP receptor), oxytocin (molecular relative to vasopressin), oxytocin receptor and vasopressin receptors (V1aR and V1bR) immunoreactive cells were higher in female compared to male rats. Vasopressin and its receptors mRNA were expressed in both hypothalamus and trigeminal ganglion; however, the vasopressin mRNA level was significantly higher in the hypothalamus.
CONCLUSIONS
A better understanding of potential hormonal influences on migraine mechanisms is needed to improve treatment of female migraineurs. It is intriguing that vasopressin is an output of hypothalamic neurons that influences areas associated with migraine. Therefore, vasopressin and the closely related oxytocin might be important hypothalamic components that contribute to migraine pathophysiology.
Topics: Female; Male; Animals; Rats; Calcitonin Gene-Related Peptide; Oxytocin; Vasopressins; Migraine Disorders; RNA, Messenger
PubMed: 36456902
DOI: 10.1186/s10194-022-01524-7 -
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 -
Membranes Jun 2023G-protein coupled receptors (GPCRs) are versatile signaling proteins that regulate key physiological processes in response to a wide variety of extracellular stimuli.... (Review)
Review
G-protein coupled receptors (GPCRs) are versatile signaling proteins that regulate key physiological processes in response to a wide variety of extracellular stimuli. The last decade has seen a revolution in the structural biology of clinically important GPCRs. Indeed, the improvement in molecular and biochemical methods to study GPCRs and their transducer complexes, together with advances in cryo-electron microscopy, NMR development, and progress in molecular dynamic simulations, have led to a better understanding of their regulation by ligands of different efficacy and bias. This has also renewed a great interest in GPCR drug discovery, such as finding biased ligands that can either promote or not promote specific regulations. In this review, we focus on two therapeutically relevant GPCR targets, the V2 vasopressin receptor (V2R) and the mu-opioid receptor (µOR), to shed light on the recent structural biology studies and show the impact of this integrative approach on the determination of new potential clinical effective compounds.
PubMed: 37367810
DOI: 10.3390/membranes13060606 -
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 -
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 -
American Journal of Physiology. Renal... Nov 2020Nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to the antidiuretic hormone arginine vasopressin (AVP), which leads to polyuria, plasma... (Review)
Review
Nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to the antidiuretic hormone arginine vasopressin (AVP), which leads to polyuria, plasma hyperosmolarity, polydipsia, and impaired quality of living. Inherited forms are caused by X-linked loss-of-function mutations in the gene encoding the vasopressin 2 receptor (V2R) or autosomal recessive/dominant mutations in the gene encoding aquaporin 2 (AQP2). A common acquired form is lithium-induced NDI. AVP facilitates reabsorption of water through increased abundance and insertion of AQP2 in the apical membrane of principal cells in the collecting ducts. In X-linked NDI, V2R is dysfunctional, which leads to impaired water reabsorption. These patients have functional AQP2, and thus the challenge is to achieve AQP2 membrane insertion independently of V2R. The current treatment is symptomatic and is based on distally acting diuretics (thiazide or amiloride) and cyclooxygenase inhibitors (indomethacin). This mini-review covers published data from trials in preclinical in vivo models and a few human intervention studies to improve NDI by more causal approaches. Promising effects on NDI in preclinical studies have been demonstrated by the use of pharmacological approaches with secretin, Wnt5a, protein kinase A agonist, fluconazole, prostaglandin E EP2 and EP4 agonists, statins, metformin, and soluble prorenin receptor agonists. In patients, only casuistic reports have evaluated the effect of statins, phosphodiesterase inhibitors (rolipram and sildenafil), and the guanylate cyclase stimulator riociguat without amelioration of symptoms. It is concluded that there is currently no established intervention that causally improves symptoms or quality of life in patients with NDI. There is a need to collaborate to improve study quality and conduct formal trials.
Topics: Animals; Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; Diabetes Mellitus; Humans; Polyuria; Protein Transport; Receptors, Vasopressin
PubMed: 32924547
DOI: 10.1152/ajprenal.00339.2020 -
Journal of Nuclear Medicine : Official... Apr 2022Arginine vasopressin is a hormone that is synthesized mainly in the hypothalamus and stored in the posterior pituitary. Receptors for vasopressin are categorized into at...
Arginine vasopressin is a hormone that is synthesized mainly in the hypothalamus and stored in the posterior pituitary. Receptors for vasopressin are categorized into at least 3 subtypes (V, V, and V). Among these subtypes, the V receptor (VR), highly expressed in the pituitary, is a primary regulator of hypothalamic-pituitary-adrenal axis activity and thus a potential target for treatment of neuropsychiatric disorders such as depression and anxiety. --butyl-2-[2-(6-methoxypyridine-2-yl)-6-[3-(morpholin-4-yl)propoxy]-4-oxopyrido[2,3-d]pyrimidin-3(4)-yl]acetamide (TASP699) is a novel PET radiotracer with high affinity and selectivity for VR. The purpose of this study was to characterize the pharmacokinetic and binding profiles of C-TASP699 in humans and determine its utility in an occupancy study of a novel VR antagonist, TS-121. Six healthy subjects were scanned twice with C-TASP699 to determine the most appropriate kinetic model for analysis of imaging data and test-retest reproducibility of outcome measures. Nine healthy subjects were scanned before and after administration of TS-121 (active component: THY1773) to assess VR occupancy. Metabolite-corrected arterial input functions were obtained. Pituitary time-activity curves were analyzed with 1- and 2-tissue-compartment (1TC and 2TC, respectively) models and multilinear analysis 1 (MA1) to calculate distribution volume (). Relative test-retest variability (TRV) and absolute TRV were calculated. Since no brain region could be used as a reference region, percentage change in after TS-121 administration was computed to assess its receptor occupancy and correlate with plasma concentrations of the drug. C-TASP699 showed high uptake in the pituitary and no uptake in any brain region. The 2TC model provided better fits than the 1TC model. Because the MA1 estimates were similar to the 2TC estimates, MA1 was the model of choice. The TRV of was good (TRV, -2% ± 14%; absolute TRV, 11%). THY1773 reduced in a dose-dependent fashion, with a half-maximal inhibitory concentration of 177 ± 52 ng/mL in plasma concentration. There were no adverse events resulting in discontinuation from the study. C-TASP699 was shown to display appropriate kinetics in humans, with substantial specific binding and good reproducibility of Therefore, this tracer is suitable for measurement of VR in the human pituitary and the VR occupancy of TS-121, a novel VR antagonist.
Topics: Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Positron-Emission Tomography; Pyridines; Pyrimidinones; Receptors, Vasopressin; Reproducibility of Results
PubMed: 34385336
DOI: 10.2967/jnumed.121.262430 -
Frontiers in Endocrinology 2020In this review, the role of oxytocin and oxytocin-like agents (acting via the oxytocin receptor and belonging to the oxytocin-family) in the male reproductive tract is... (Review)
Review
In this review, the role of oxytocin and oxytocin-like agents (acting via the oxytocin receptor and belonging to the oxytocin-family) in the male reproductive tract is considered. Previous research (dating back over 60 years) is revised and connected with recently found aspects of the role oxytocin plays in male reproductive health. The local expression of oxytocin and its receptor in the male reproductive tract of different species is summarized. Colocalization and possible crosstalk to other agents and receptors and their resulting effects are discussed. The role of the newly reported oxytocin focused signaling pathways in the male reproductive tract, other than mediating contractility, is critically examined. The structure and effect of the most promising oxytocin-agonists and -antagonists are reviewed for their potential in treating male disorders with origins in the male reproductive tract such as prostate diseases and ejaculatory disorders.
Topics: Animals; Arginine Vasopressin; Genitalia, Male; Hormone Antagonists; Humans; Male; Oxytocin; Prostatic Neoplasms; Receptors, Oxytocin; Signal Transduction
PubMed: 33193084
DOI: 10.3389/fendo.2020.565731 -
Frontiers in Neuroendocrinology Oct 2018Oxytocin (OT) and arginine-vasopressin (AVP) act in the brain to regulate social cognition/social behavior and in the periphery to influence a variety of physiological... (Review)
Review
Oxytocin (OT) and arginine-vasopressin (AVP) act in the brain to regulate social cognition/social behavior and in the periphery to influence a variety of physiological processes. Although the chemical structures of OT and AVP as well as their receptors are quite similar, OT and AVP can have distinct or even opposing actions. Here, we review the increasing body of evidence that exogenously administered and endogenously released OT and AVP can activate each other's canonical receptors (i.e., cross-talk) and examine the possibility that receptor cross-talk following the synaptic and non-synaptic release of OT and AVP contributes to their distinct roles in the brain and periphery. Understanding the consequences of cross-talk between OT and AVP receptors will be important in identifying how these peptides control social cognition and behavior and for the development of drugs to treat a variety of psychiatric disorders.
Topics: Animals; Arginine Vasopressin; Female; Humans; Male; Mental Disorders; Oxytocin; Receptors, Oxytocin; Receptors, Vasopressin; Social Behavior
PubMed: 29054552
DOI: 10.1016/j.yfrne.2017.10.004