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Annals of Nutrition & Metabolism 2018Diabetic nephropathy has become the most common cause of chronic kidney disease (CKD). Despite the progress accomplished in therapy, the prevalence of renal disorders... (Review)
Review
BACKGROUND
Diabetic nephropathy has become the most common cause of chronic kidney disease (CKD). Despite the progress accomplished in therapy, the prevalence of renal disorders remains high. Some modifiable factors driving the increase in incidence of CKD, in diabetes and other settings, might have been overlooked. Consistent evidence supports a role for vasopressin, hydration state, and urine concentration in kidney health.
SUMMARY
Plasma vasopressin is elevated in diabetes, even if metabolic control is good. Several epidemiological studies have pointed to a positive association between markers of vasopressin secretion (24-h fluid intake, urine volume, plasma copeptin concentration) and renal function decline in both the community and populations at high risk of CKD, namely, diabetic patients. Research involving animal models also supports a critical causal role of the V2 receptor antidiuretic effects of vasopressin in the early signs of kidney disease associated with type 1 or type 2 diabetes. Key Messages: Data supporting the detrimental effects of chronic vasopressin action on the kidney is consistent in animal models and human observational studies. Since vasopressin secretion can be modulated by water intake, and its actions by selective receptor antagonists, the vasopressin-hydration system could be a potential therapeutic target for the prevention and treatment of diabetic nephropathy. Intervention studies are needed to examine the relevance of lifestyle or pharmacological interventions.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Drinking; Glycopeptides; Humans; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Vasopressins
PubMed: 29925069
DOI: 10.1159/000488124 -
British Journal of Pharmacology Apr 2022Oxytocin (OT) and vasopressin (AVP) are endogenous ligands for OT and AVP receptors in the brain and in the peripheral system. Several studies demonstrate that OT and... (Review)
Review
Oxytocin (OT) and vasopressin (AVP) are endogenous ligands for OT and AVP receptors in the brain and in the peripheral system. Several studies demonstrate that OT and AVP have opposite roles in modulating stress, anxiety and social behaviours. Interestingly, both peptides and their receptors exhibit high sequence homology which could account for the biased signalling interaction of the peptides with OT and AVP receptors. However, how and under which conditions this crosstalk occurs in vivo remains unclear. In this review we shed light on the complexity of the roles of OT and AVP, by focusing on their signalling and behavioural differences and exploring the crosstalk between the receptor systems. Moreover, we discuss the potential of OT and AVP receptors as therapeutic targets to treat human disorders, such as autism, schizophrenia and drug abuse. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.
Topics: Brain; Humans; Ligands; Oxytocin; Receptors, Oxytocin; Receptors, Vasopressin; Social Behavior; Vasopressins
PubMed: 33817785
DOI: 10.1111/bph.15481 -
The International Journal of... Jul 2021Accumulating evidence shows that certain populations of depressed patients have impaired hypothalamus-pituitary-adrenal (HPA) axis function. Arginine-vasopressin (AVP)... (Review)
Review
Accumulating evidence shows that certain populations of depressed patients have impaired hypothalamus-pituitary-adrenal (HPA) axis function. Arginine-vasopressin (AVP) is one of the primary factors in HPA axis regulation under stress situations, and AVP and its receptor subtype (V1B receptor) play a pivotal role in HPA axis abnormalities observed in depression. Based on this hypothesis, several non-peptide V1B receptor antagonists have been synthesized, and the efficacies of some V1B receptor antagonists have been investigated in both animals and humans. V1B receptor antagonists exert antidepressant-like effects in several animal models at doses that attenuate the hyperactivity of the HPA axis, and some of their detailed mechanisms have been delineated. These results obtained in animal models were, at least partly, reproduced in clinical trials. At least 2 V1B receptor antagonists (TS-121 and ABT-436) showed tendencies to reduce the depression scores of patients with major depressive disorder at doses that attenuate HPA axis hyperactivity or block the pituitary V1B receptor. Importantly, TS-121 showed a clearer efficacy for patients with higher basal cortisol levels than for those with lower basal cortisol levels, which was consistent with the hypothesis that V1B receptor antagonists may be more effective for patients with HPA axis hyperactivity. Therefore, V1B receptor antagonists are promising approaches for the treatment of depression involving HPA axis impairment such as depression.
Topics: Animals; Antidepressive Agents; Antidiuretic Hormone Receptor Antagonists; Depressive Disorder, Major; Humans; Hypothalamo-Hypophyseal System; Receptors, Vasopressin
PubMed: 33733667
DOI: 10.1093/ijnp/pyab013 -
American Journal of Physiology. Renal... Jan 2024Tolvaptan, a vasopressin antagonist selective for the V2-subtype vasopressin receptor (V2R), is widely used in the treatment of hyponatremia and autosomal-dominant...
Tolvaptan, a vasopressin antagonist selective for the V2-subtype vasopressin receptor (V2R), is widely used in the treatment of hyponatremia and autosomal-dominant polycystic kidney disease (ADPKD). Its effects on signaling in collecting duct cells have not been fully characterized. Here, we perform RNA-seq in a collecting duct cell line (mpkCCD). The data show that tolvaptan inhibits the expression of mRNAs that were previously shown to be increased in response to vasopressin including aquaporin-2, but also reveals mRNA changes that were not readily predictable and suggest off-target actions of tolvaptan. One such action is activation of the MAPK kinase (ERK1/ERK2) pathway. Prior studies have shown that ERK1/ERK2 activation is essential in the regulation of a variety of cellular and physiological processes and can be associated with cell proliferation. In immunoblotting experiments, we demonstrated that ERK1/ERK2 phosphorylation in mpkCCD cells was significantly reduced by vasopressin, in contrast to the increases seen in non-collecting-duct cells overexpressing V2R in prior studies. We also found that tolvaptan has a strong effect to increase ERK1/ERK2 phosphorylation in the presence of vasopressin and that tolvaptan's effect to increase ERK1/ERK2 phosphorylation is absent in mpkCCD cells in which both protein kinase A (PKA)-catalytic subunits have been deleted. Thus, it appears that the tolvaptan effect to increase ERK activation is PKA-dependent and is not due to an off-target effect of tolvaptan. We conclude that in cells expressing V2R at endogenous levels: ) vasopressin decreases ERK1/ERK2 activation; ) in the presence of vasopressin, tolvaptan increases ERK1/ERK2 activation; and ) these effects are PKA-dependent. Vasopressin is a key hormone that regulates the function of the collecting duct of the kidney. ERK1 and ERK2 are enzymes that play key roles in physiological regulation in all cells. The authors used collecting duct cell cultures to investigate the effects of vasopressin and the vasopressin receptor antagonist tolvaptan on ERK1 and ERK2 phosphorylation and activation.
Topics: Tolvaptan; Receptors, Vasopressin; Phosphorylation; MAP Kinase Signaling System; Kidney; Antidiuretic Hormone Receptor Antagonists; Vasopressins
PubMed: 37916285
DOI: 10.1152/ajprenal.00124.2023 -
Frontiers in Endocrinology 2023The diabetic kidney disease (DKD) is the major cause of the chronic kidney disease (CKD). Enhanced plasma vasopressin (VP) levels have been associated with the... (Review)
Review
The diabetic kidney disease (DKD) is the major cause of the chronic kidney disease (CKD). Enhanced plasma vasopressin (VP) levels have been associated with the pathophysiology of DKD and CKD. Stimulation of VP release in DKD is caused by glucose-dependent reset of the osmostat leading to secondary pathophysiologic effects mediated by distinct VP receptor types. VP is a stress hormone exhibiting the antidiuretic action in the kidney along with broad adaptive effects in other organs. Excessive activation of the vasopressin type 2 (V2) receptor in the kidney leads to glomerular hyperfiltration and nephron loss, whereas stimulation of vasopressin V1a or V1b receptors in the liver, pancreas, and adrenal glands promotes catabolic metabolism for energy mobilization, enhancing glucose production and aggravating DKD. Increasing availability of selective VP receptor antagonists opens new therapeutic windows separating the renal and extra-renal VP effects for the concrete applications. Improved understanding of these paradigms is mandatory for further drug design and translational implementation. The present concise review focuses on metabolic effects of VP affecting DKD pathophysiology.
Topics: Humans; Diabetic Nephropathies; Vasopressins; Receptors, Vasopressin; Renal Insufficiency, Chronic; Glucose; Diabetes Mellitus
PubMed: 37790608
DOI: 10.3389/fendo.2023.1176199 -
Journal of Neuroendocrinology Apr 2016In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using... (Review)
Review
In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using a suite of methodologies, including electrophysiology, site-specific selective pharmacology, receptor autoradiography, in vivo microdialysis, and genetic and optogenetic manipulations, we have gained unprecedented knowledge about how these neuropeptides engage neural circuits to regulate behaviour, particularly social behaviour. Based on this foundation of information from rodent studies, we have started generating new hypotheses and frameworks about how the oxytocin and vasopressin systems could be acting in humans to influence social cognition. However, despite the recent inundation of publications using intranasal oxytocin in humans, we still know very little about the neurophysiology of the oxytocin system in primates more broadly. Furthermore, the design and analysis of these human studies have remained largely uninformed of the potential neurobiological mechanisms underlying their findings. Although the methods available for studying the oxytocin and vasopressin systems in humans are incredibly limited as a result of practical and ethical considerations, there is great potential to fill the gaps in our knowledge by developing better nonhuman primate models of social functioning. Behavioural pharmacology and receptor autoradiography have been used to study the oxytocin and vasopressin systems in nonhuman primates, and there is now great potential to broaden our understanding of the neurobiology of these systems. In this review, we discuss comparative findings in receptor distributions in rodents and primates, with perspectives on the functionality of conserved regions of expression in these distinct mammalian clades. We also identify specific ways that established technologies can be used to answer basic research questions in primates. Finally, we highlight areas of future research in nonhuman primates that are experimentally poised to yield critical insights into the anatomy, physiology and behavioural effects of the oxytocin system, given its remarkable translational potential.
Topics: Animals; Receptors, Oxytocin; Receptors, Vasopressin; Species Specificity; Translational Research, Biomedical
PubMed: 26940141
DOI: 10.1111/jne.12382 -
Frontiers in Endocrinology 2023The diluting and concentrating function of the kidney plays a crucial role in regulating the water homeostasis of the body. This function is regulated by the... (Review)
Review
The diluting and concentrating function of the kidney plays a crucial role in regulating the water homeostasis of the body. This function is regulated by the antidiuretic hormone, arginine vasopressin through the type 2 vasopressin receptor (V2R), allowing the body to adapt to periods of water load or water restriction. Loss-of-function mutations of the V2R cause X-linked nephrogenic diabetes insipidus (XNDI), which is characterized by polyuria, polydipsia, and hyposthenuria. Gain-of-function mutations of the V2R lead to nephrogenic syndrome of inappropriate antidiuresis disease (NSIAD), which results in hyponatremia. Various mechanisms may be responsible for the impaired receptor functions, and this review provides an overview of recent findings about the potential therapeutic interventions in the light of the current experimental data.
Topics: Receptors, Vasopressin; Vasopressins; Mutation; Water; Molecular Biology
PubMed: 37293495
DOI: 10.3389/fendo.2023.1173601 -
Cellular Signalling Mar 2016Heart failure (HF) continues to be a highly prevalent syndrome, affecting millions of patients and costing billions of dollars in treatment per year in the United States... (Review)
Review
Heart failure (HF) continues to be a highly prevalent syndrome, affecting millions of patients and costing billions of dollars in treatment per year in the United States alone. Studies in failing human heart and in transgenic HF models led to the recognition that enhanced neurohormonal signaling plays a causative role in HF progression, and the use of neurohormone receptor antagonists have proven to decrease hospitalization rates. It has also been long recognized that patients with HF have abnormal water retention, hypo-osmolality, and hyponatremia secondary to elevations in the levels of the neurohormone arginine vasopressin (AVP). AVP is released from the hypothalamus in response to changes in plasma osmolality and pressure, acting at three distinct G protein-coupled receptors: V1AR, V1BR and V2R. Persistent AVP release causes hyponatremia via renal V2R activation, a risk factor for death and hospitalization, and there is a correlation between plasma AVP levels and HF severity/survival of chronic HF patients. Because of the adverse clinical consequences associated with the development of hyponatremia, V2R antagonists were developed for the treatment of HF patients with hyponatremia, however in contrast to other neurohormone blockers they do not relay a survival benefit and may exacerbate decompensated HF requiring inotropic support. Renewed interest in the cardiac V1AR system during HF has arisen due to several recent findings: 1) mice with myocyte-selective transgenic overexpression of cardiac V1AR developed cardiomyopathy in the absence of any pathological insult, 2) cardiac V1AR expression was shown to be increased late-stage human HF, and 3) V1AR antagonism prevented cardiomyopathy development in a mouse model of HF. While cardiac V1AR expression is increased in HF, the role of V1AR signaling in various forms of cardiac injury and in distinct cardiac cell types has been controversial. Therefore this review will primarily focus on V1AR signaling as a potential therapeutic target for HF treatment.
Topics: Animals; Fibroblasts; Heart Failure; Humans; Kidney; Muscle, Smooth, Vascular; Myocytes, Cardiac; Receptors, Vasopressin; Signal Transduction
PubMed: 26232615
DOI: 10.1016/j.cellsig.2015.07.021 -
Life Science Alliance Apr 2023Specific receptors for the neurohypophyseal hormones, arginine vasopressin (AVP) and oxytocin, are present in the male reproductive organs. However, their exact roles...
Specific receptors for the neurohypophyseal hormones, arginine vasopressin (AVP) and oxytocin, are present in the male reproductive organs. However, their exact roles remain unknown. To elucidate the physiological functions of pituitary hormones in male reproduction, this study first focused on the distribution and function of one of the AVP receptors, V1a. In situ hybridization analysis revealed high expression of the in Leydig cells of the testes and narrow/clear cells in the epididymis, with the expression pattern differing from that of the oxytocin receptor (OTR). Notably, persistent motility and highly proportional hyperactivation were observed in spermatozoa from V1a receptor-deficient mice. In contrast, OTR blocking by antagonist atosiban decreased hyperactivation rate. Furthermore, AVP stimulation could alter the extracellular pH mediated by the V1a receptor. The results highlight the crucial role of neurohypophyseal hormones in male reproductive physiology, with potential contradicting roles of V1a and OTR in sperm maturation. Our findings suggest that V1a receptor antagonists are potential therapeutic drugs for male infertility.
Topics: Male; Mice; Animals; Receptors, Oxytocin; Receptors, Vasopressin; Sperm Motility; Semen; Oxytocin; Arginine Vasopressin
PubMed: 36650057
DOI: 10.26508/lsa.202201488 -
Frontiers in Neuroendocrinology Apr 2019Vasopressin (AVP) and oxytocin (OXT) regulate social behavior by binding to their canonical receptors, the vasopressin V1a receptor (V1aR) and oxytocin receptor (OTR),... (Review)
Review
Vasopressin (AVP) and oxytocin (OXT) regulate social behavior by binding to their canonical receptors, the vasopressin V1a receptor (V1aR) and oxytocin receptor (OTR), respectively. Recent studies suggest that these neuropeptides may also signal via each other's receptors. The extent to which such cross-system signaling occurs likely depends on anatomical overlap between AVP/OXT fibers and V1aR/OTR expression. By comparing AVP/OXT fiber densities with V1aR/OTR binding densities throughout the rat social behavior neural network (SBNN), we propose the potential for cross-system signaling in four regions: the medial amygdala (MeA), bed nucleus of the stria terminalis (BNSTp), medial preoptic area, and periaqueductal grey. We also discuss possible implications of corresponding sex (higher in males versus females) and age (higher in adults versus juveniles) differences in AVP fiber and OTR binding densities in the MeA and BNSTp. Overall, this review reveals the need to unravel the consequences of potential cross-system signaling between AVP and OXT systems in the SBNN for the regulation of social behavior.
Topics: Animals; Humans; Nerve Net; Oxytocin; Receptors, Oxytocin; Receptors, Vasopressin; Social Behavior; Vasopressins
PubMed: 30753840
DOI: 10.1016/j.yfrne.2019.02.001