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Hormones and Behavior Feb 2023Genetic knockouts of the vasopressin receptor 1a (Avpr1a), oxytocin receptor (Oxtr), or oxytocin (Oxt) gene in mice have helped cement the causal relationship between...
Genetic knockouts of the vasopressin receptor 1a (Avpr1a), oxytocin receptor (Oxtr), or oxytocin (Oxt) gene in mice have helped cement the causal relationship between these neuropeptide systems and various social behaviors (e.g., social investigation, recognition, and communication, as well as territoriality and aggression). In mice, these social behaviors depend upon the olfactory system. Thus, it is critical to assess the olfactory capabilities of these knockout models to accurately interpret the observed differences in social behavior. Prior studies utilizing these transgenic mice have sought to test for baseline deficits in olfactory processing; predominantly through use of odor habituation/dishabituation tasks, buried food tests, or investigation assays using non-social odorants. While informative, these assays rely on the animal's intrinsic motivation and locomotor behavior to measure olfactory capabilities and thus, often yield mixed results. Instead, psychophysical analyses using operant conditioning procedures and flow-dilution olfactometry are ideally suited to precisely quantify olfactory perception. In the present study, we used these methods to assess the main olfactory capabilities of adult male and female Avpr1a, Oxtr, and Oxt transgenic mice to volatile non-social odorants. Our results indicate that homozygous and heterozygous knockout mice of all three strains have the same sensitivity and discrimination ability as their wild-type littermates. These data strongly support the hypothesis that the observed social deficits of these global knockout mice are not due to baseline deficits of their main olfactory system.
Topics: Mice; Male; Female; Animals; Receptors, Oxytocin; Oxytocin; Odorants; Receptors, Vasopressin; Social Behavior; Mice, Transgenic; Mice, Knockout
PubMed: 36628861
DOI: 10.1016/j.yhbeh.2022.105302 -
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 -
International Journal of Molecular... Mar 2022Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is... (Review)
Review
Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Over years, many attempts have been made to modify this hormone and find AVP analogues with different pharmacological profiles that could overcome its limitations. Non-peptide AVP analogues with low molecular weight presented good affinity to AVP receptors. Natural peptide counterparts, found in animals, are successfully applied as therapeutics; for instance, lypressin used in treatment of diabetes insipidus. Synthetic peptide analogues compensate for the shortcomings of AVP. Desmopressin is more resistant to proteolysis and presents mainly antidiuretic effects, while terlipressin is a long-acting AVP analogue and a drug recommended in the treatment of varicose bleeding in patients with liver cirrhosis. Recently published results on diverse applications of AVP analogues in medicinal practice, including potential lypressin, terlipressin and ornipressin in the treatment of SARS-CoV-2, are discussed.
Topics: Animals; Antidiuretic Agents; COVID-19; Deamino Arginine Vasopressin; Diabetes Insipidus; Hemostatics; Humans; Lypressin; Molecular Structure; Ornipressin; Pandemics; SARS-CoV-2; Terlipressin; Vasopressins; COVID-19 Drug Treatment
PubMed: 35328489
DOI: 10.3390/ijms23063068 -
Journal of Neuroendocrinology Feb 2022Social recognition is an essential skill for the expression of appropriate behaviors towards conspecifics in most social species. Several studies point to oxytocin (OT)... (Review)
Review
Social recognition is an essential skill for the expression of appropriate behaviors towards conspecifics in most social species. Several studies point to oxytocin (OT) and arginine vasopressin (AVP) as key mediators of social recognition in males and females. However, sex differences in social cognitive behaviors highlight an important interplay between OT, AVP and the sex steroids. Estrogens facilitate social recognition by regulating OT action in the hypothalamus and that of OT receptor in the medial amygdala. The role of OT in these brain regions appears to be essential for social recognition in both males and females. Conversely, social recognition in male rats and mice is more dependent on AVP release in the lateral septum than in females. The AVP system comprises a series of highly sexually dimorphic brain nuclei, including the bed nucleus of the stria terminalis, the amygdala and the lateral septum. Various studies suggest that testosterone and its metabolites, including estradiol, influence social recognition in males by modulating the activity of the AVP at V1a receptor. Intriguingly, both estrogens and androgens can affect social recognition very rapidly, through non-genomic mechanisms. In addition, the androgen metabolites, namely 3α-diol and 3β-diol, may also have an impact on social behaviors either by interacting with the estrogen receptors or through other mechanisms. Overall, the regulation of OT and AVP by sex steroids fine tunes social recognition and the behaviors that depend upon it (e.g., social bond, hierarchical organization, aggression) in a sex-dependent manner. Elucidating the sex-dependent interaction between sex steroids and neuroendocrine systems is essential for understanding sex differences in the normal and abnormal expression of social behaviors.
Topics: Androgens; Animals; Arginine Vasopressin; Estrogens; Female; Gonadal Steroid Hormones; Male; Mice; Neurosecretory Systems; Oxytocin; Rats; Receptors, Oxytocin; Social Behavior; Steroids
PubMed: 34927288
DOI: 10.1111/jne.13070 -
The role of oxytocin, vasopressin, and their receptors at nociceptors in peripheral pain modulation.Frontiers in Neuroendocrinology Oct 2021Oxytocin and vasopressin are neurohypophyseal hormones with sequence similarity and play a central role in bodily homeostatic regulation. Pain is currently understood to... (Review)
Review
Oxytocin and vasopressin are neurohypophyseal hormones with sequence similarity and play a central role in bodily homeostatic regulation. Pain is currently understood to be an important phenotype that those two neurohormones strongly downregulate. Nociceptors, the first component of the ascending neural circuit for pain signals, have constantly been shown to be modulated by those peptides. The nociceptor modulation appears to be critical in pain attenuation, which has led to a gradual increase in scientific interest about their physiological processes and also drawn attention to their translational potentials. This review focused on what are recently understood and stay under investigation in the functional modulation of nociceptors by oxytocin and vasopressin. Effort to produce a nociceptor-specific view could help to construct a more systematic picture of the peripheral pain modulation by oxytocin and vasopressin.
Topics: Humans; Nociceptors; Oxytocin; Pain; Receptors, Oxytocin; Receptors, Vasopressin; Vasopressins
PubMed: 34437871
DOI: 10.1016/j.yfrne.2021.100942 -
Molecular Neurobiology Oct 2019Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by a typical brain edema. Its pathogenesis is still debated through... (Review)
Review
Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by a typical brain edema. Its pathogenesis is still debated through hypoperfusion and hyperperfusion theories, which have many limitations. As PRES occurs almost exclusively in clinical situations with arginine vasopressin (AVP) hypersecretion, such as eclampsia and sepsis, we hypothesize that AVP plays a central pathophysiologic role. In this review, we discuss the genesis of PRES and its symptoms through this novel approach. We theorize that AVP axis stimulation precipitates PRES development through an increase in AVP secretion or AVP receptor density. Activation of vasopressin V receptors leads to cerebral vasoconstriction, causing endothelial dysfunction and cerebral ischemia. This promotes cytotoxic edema through hydromineral transglial flux dysfunction and may increase endothelial permeability, leading to subsequent vasogenic brain edema. If our hypothesis is confirmed, it opens new perspectives for better patient monitoring and therapies targeting the AVP axis in PRES.
Topics: Animals; Arginine Vasopressin; Biomarkers; Comorbidity; Disease Susceptibility; Humans; Models, Biological; Posterior Leukoencephalopathy Syndrome
PubMed: 30924075
DOI: 10.1007/s12035-019-1553-y -
Stress (Amsterdam, Netherlands) Nov 2020Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with a wide range of behavioral disturbances and serious consequences for both patient and...
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with a wide range of behavioral disturbances and serious consequences for both patient and society. One of the main reasons for unsuccessful therapies is insufficient knowledge about its underlying pathomechanism. In the search for centrally signaling molecules that might be relevant to the development of PTSD we focus here on arginine vasopressin (AVP). So far AVP has not been strongly implicated in PTSD, but different lines of evidence suggest a possible impact of its signaling in all clusters of PTSD symptomatology. More specifically, in laboratory rodents, AVP agonists affect behavior in a PTSD-like manner, while significant reduction of AVP signaling in the brain e.g. in AVP-deficient Brattleboro rats, ameliorated defined behavioral parameters that can be linked to PTSD symptoms. Different animal models of PTSD also show alterations in the AVP signaling in distinct brain areas. However, pharmacological treatment targeting central AVP receptors via systemic routes is hampered by possible side effects that are linked to the peripheral action of AVP as a hormone. Indeed, the V1a receptor, the most common receptor subtype in the brain, is implicated in vasoconstriction. Thus, systemic treatment with V1a receptor antagonists would be implicated in hypotonia. This implies that novel treatment concepts are needed to target AVP receptors not only at brain level but also in distinct brain areas, to offer alternative treatments for PTSD.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Humans; Rats; Rats, Brattleboro; Receptors, Vasopressin; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins
PubMed: 33043781
DOI: 10.1080/10253890.2020.1826430 -
Turkish Journal of Anaesthesiology and... Aug 2023Vasoplegic syndrome (VS) is defined as low systemic vascular resistance, normal or high cardiac output, and resistant hypotension unresponsive to vasopressor agents and...
Vasoplegic syndrome (VS) is defined as low systemic vascular resistance, normal or high cardiac output, and resistant hypotension unresponsive to vasopressor agents and intravenous volume. VS is a frequently encountered complication in cardiovascular and transplantation surgery, burns, trauma, pancreatitis, and sepsis. The basis of the pathophysiology is associated with an imbalance of vasodilator and vasoconstrictive structure in vascular smooth muscle cells and is highly complex. The pathogenesis of VS has several mechanisms, including overproduction of iNO, stimulation of ATP-dependent K+ channels and NF-κB, and vasopressin receptor 1A (V1A-receptor) down-regulation. Available treatments involve volume and inotropes administration, vasopressin, methylene blue, hydroxocobalamin, Ca++, vitamin C, and thiamine, and should also restore vascular tone and improve vasoplegia. Other treatments could include angiotensin II, corticosteroids, NF-κB inhibitor, ATP-dependent K+ channel blocker, indigo carmine, and hyperbaric oxygen therapy. Despite modern advances in treatment, the mortality rate is still 30-50%. It is challenging for an anaesthesiologist to consider this syndrome's diagnosis and manage its treatment. Our review aims to review the diagnosis, predisposing factors, pathophysiology, treatment, and anaesthesia approach of VS during anaesthesia and to suggest a treatment algorithm.
PubMed: 37587654
DOI: 10.4274/TJAR.2023.221093 -
The Journal of Laryngology and Otology Dec 2023This study aimed to determine the distribution and subcellular localisation of aquaporin 2 and vasopressin type 2 receptor in the human endolymphatic sac.
OBJECTIVE
This study aimed to determine the distribution and subcellular localisation of aquaporin 2 and vasopressin type 2 receptor in the human endolymphatic sac.
METHODS
Ten samples of human endolymphatic sac were collected during acoustic neurinoma removal using the translabyrinthine approach. Immunohistochemistry and immunofluorescence were performed using aquaporin 2 and vasopressin type 2 receptor monoclonal antibodies.
RESULTS
Confocal microscopy demonstrated that vasopressin type 2 receptor labelling was expressed in both the apical and basolateral plasma membranes, and in the cytoplasm of the endolymphatic sac epithelium, whereas aquaporin 2 was strongly expressed at the basolateral site of the endolymphatic sac epithelium, in both the intraosseous and extraosseous parts of the endolymphatic sac.
CONCLUSION
Both aquaporin 2 and vasopressin type 2 receptor were detected in the epithelial cells of the human endolymphatic sac, suggesting that this channel may be involved in inner-ear fluid homeostasis. However, strong basolateral expression of aquaporin 2 in endolymphatic sac epithelium suggested that the function of aquaporin 2 may differ between the endolymphatic sac and kidney.
Topics: Humans; Endolymphatic Sac; Aquaporin 2; Receptors, Vasopressin; Vasopressins
PubMed: 36502818
DOI: 10.1017/S0022215122002444 -
Revue Medicale Suisse Apr 2020Vasopressin (AVP) is a posterior pituitary hormone initially known for its antidiuretic actions. In this article, we recall the biochemical and pharmacological... (Review)
Review
Vasopressin (AVP) is a posterior pituitary hormone initially known for its antidiuretic actions. In this article, we recall the biochemical and pharmacological characteristics of the AVP and its analogues. Currently, its main indication in critical care medicine is vasoplegic shock in view of its vasopressive properties. This strong vasopressive activity is related to the activation of V1 receptors located in the vascular smooth muscle. The scientific evidence of the AVP therapy, and its potential benefits versus norepinephrine in vasoplegic shock, is reviewed in this article. Similarly, we present the other indications of vasopressin in the critical patient, based on recent studies and international guidelines.
Topics: Arginine Vasopressin; Critical Illness; Humans; Muscle, Smooth, Vascular; Norepinephrine; Receptors, Vasopressin; Vasoplegia
PubMed: 32239840
DOI: No ID Found