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Neuroscience Jul 2023The nonapeptide system modulates a diversity of social behaviors, including aggression, parental care, affiliation, sexual behavior, and pair bonding. Such social...
The nonapeptide system modulates a diversity of social behaviors, including aggression, parental care, affiliation, sexual behavior, and pair bonding. Such social behaviors are regulated through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin V1a receptor (AVPR1A) in the brain. Nonapeptide receptor distributions have been mapped for several species, however, studies have demonstrated that there is substantial variation across species. Mongolian gerbils (Meriones unguiculatus) are an excellent organism for studying family dynamics, social development, pair bonding, and territorial aggression. Although an increasing number of studies are examining the neural mechanisms of social behavior in Mongolian gerbils, nonapeptide receptor distributions have yet to be characterized for this species. Here we conducted receptor autoradiography to map distributions of OXTR and AVPR1A binding throughout the basal forebrain and midbrain of female and male Mongolian gerbils. Further, we assessed whether gonadal sex influenced binding densities in brain regions important for social behavior and reward, however, we observed no effects of sex on OXTR or AVPR1A binding densities. These findings provide mapping distributions of nonapeptide receptors in male and female Mongolian gerbils, laying a foundation for future studies that seek to manipulate the nonapeptide system to examine nonapeptide-mediated social behavior.
Topics: Animals; Male; Female; Receptors, Oxytocin; Gerbillinae; Basal Forebrain; Vasopressins; Mesencephalon; Receptors, Vasopressin; Oxytocin; Social Behavior; DNA-Binding Proteins
PubMed: 37172688
DOI: 10.1016/j.neuroscience.2023.05.004 -
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 -
Annals of Intensive Care Jan 2020Activation of arginine-vasopressin is one of the hormonal responses to face vasodilation-related hypotension. Released from the post-pituitary gland, vasopressin induces... (Review)
Review
Activation of arginine-vasopressin is one of the hormonal responses to face vasodilation-related hypotension. Released from the post-pituitary gland, vasopressin induces vasoconstriction through the activation of V1a receptors located on vascular smooth muscle cells. Due to its non-selective receptor affinity arginine-vasopressin also activates V2 (located on renal tubular cells of collecting ducts) and V1b (located in the anterior pituitary and in the pancreas) receptors, thereby potentially promoting undesired side effects such as anti-diuresis, procoagulant properties due to release of the von Willebrand's factor and platelet activation. Finally, it also cross-activates oxytocin receptors. During septic shock, vasopressin plasma levels were reported to be lower than expected, and a hypersensitivity to its vasopressor effect is reported in such situation. Terlipressin and selepressin are synthetic vasopressin analogues with a higher affinity for the V1 receptor, and, hence, potentially less side effects. In this narrative review, we present the current knowledge of the rationale, benefits and risks of vasopressin use in the setting of septic shock and vasoplegic shock following cardiac surgery. Clearly, vasopressin administration allows reducing norepinephrine requirements, but so far, no improvement of survival was reported and side effects are frequent, particularly ischaemic events. Finally, we will discuss the current indications for vasopressin and its agonists in the setting of septic shock, and the remaining unresolved questions.
PubMed: 31970567
DOI: 10.1186/s13613-020-0628-2 -
Revista Medica Del Instituto Mexicano... Mar 2023Oxytocin and vasopressin share a similar chemical structure but have different functions. Both hormones are produced in different brain areas, are transported through... (Review)
Review
Oxytocin and vasopressin share a similar chemical structure but have different functions. Both hormones are produced in different brain areas, are transported through the hypophyseal portal system, pass to the anterior hypophysis, and released to reach their target organs. These hormones also act as neuromodulators, where its receptors are found in the lateral septum, the middle amygdala, the hippocampus, the hypothalamus, and the brain stem. These brain structures regulate socio-sexual behaviors in vertebrates. Moreover, the oxytocinergic and the vasopressin systems are sexually different. The sexual steroids promote oxytocin release and the oxytocin receptor synthesis, as well as promoting or inhibiting vasopressin release and its receptor genetic transcription. Both neuropeptides are involved in social recognition, male-female pair bonding, aggression, and cognition. Furthermore, the disruption or malfunctioning of the oxytocin and vasopressin systems adds to the causes of some psychiatric disorders like depression, schizophrenia, autism, and borderline personality.
Topics: Animals; Female; Humans; Male; Brain; Oxytocin; Schizophrenia; Vasopressins
PubMed: 37200960
DOI: No ID Found -
Biomedicines Sep 2023Autism spectrum disorder (ASD) is rather common, presenting with prevalent early problems in social communication and accompanied by repetitive behavior. As vasopressin... (Review)
Review
Autism spectrum disorder (ASD) is rather common, presenting with prevalent early problems in social communication and accompanied by repetitive behavior. As vasopressin was implicated not only in salt-water homeostasis and stress-axis regulation, but also in social behavior, its role in the development of ASD might be suggested. In this review, we summarized a wide range of problems associated with ASD to which vasopressin might contribute, from social skills to communication, motor function problems, autonomous nervous system alterations as well as sleep disturbances, and altered sensory information processing. Beside functional connections between vasopressin and ASD, we draw attention to the anatomical background, highlighting several brain areas, including the paraventricular nucleus of the hypothalamus, medial preoptic area, lateral septum, bed nucleus of stria terminalis, amygdala, hippocampus, olfactory bulb and even the cerebellum, either producing vasopressin or containing vasopressinergic receptors (presumably V). Sex differences in the vasopressinergic system might underline the male prevalence of ASD. Moreover, vasopressin might contribute to the effectiveness of available off-label therapies as well as serve as a possible target for intervention. In this sense, vasopressin, but paradoxically also V receptor antagonist, were found to be effective in some clinical trials. We concluded that although vasopressin might be an effective candidate for ASD treatment, we might assume that only a subgroup (e.g., with stress-axis disturbances), a certain sex (most probably males) and a certain brain area (targeting by means of virus vectors) would benefit from this therapy.
PubMed: 37892977
DOI: 10.3390/biomedicines11102603 -
ELife Oct 2023The vasopressin type 2 receptor (VR) is an essential G protein-coupled receptor (GPCR) in renal regulation of water homeostasis. Upon stimulation, the VR activates Gα...
The vasopressin type 2 receptor (VR) is an essential G protein-coupled receptor (GPCR) in renal regulation of water homeostasis. Upon stimulation, the VR activates Gα and Gα, which is followed by robust recruitment of β-arrestins and receptor internalization into endosomes. Unlike canonical GPCR signaling, the β-arrestin association with the VR does not terminate Gα activation, and thus, Gα-mediated signaling is sustained while the receptor is internalized. Here, we demonstrate that this VR ability to co-interact with G protein/β-arrestin and promote endosomal G protein signaling is not restricted to Gα, but also involves Gα. Furthermore, our data imply that β-arrestins potentiate Gα/Gα activation at endosomes rather than terminating their signaling. Surprisingly, we found that the VR internalizes and promote endosomal G protein activation independent of β-arrestins to a minor degree. These new observations challenge the current model of endosomal GPCR signaling and suggest that this event can occur in both β-arrestin-dependent and -independent manners.
Topics: beta-Arrestins; Receptors, Vasopressin; Arrestins; beta-Arrestin 1; Endosomes; GTP-Binding Proteins; Vasopressins
PubMed: 37855711
DOI: 10.7554/eLife.87754 -
Proceedings. Biological Sciences Jun 2023Although numerous studies have focused on brain functions related to inequity aversion, few have examined its genetic basis. Here, we show the association between...
Although numerous studies have focused on brain functions related to inequity aversion, few have examined its genetic basis. Here, we show the association between estimated inequity aversion and polymorphisms in three genes associated with human sociality. Non-student adult participants took part in five economic game experiments on different days. Disadvantageous inequity aversion (DIA) and advantageous inequity aversion (AIA) were calculated from behavioural responses using Bayesian estimation. We investigated the association between genetic polymorphisms in the oxytocin receptor ( rs53576), arginine vasopressin receptor 1A ( RS3) and opioid receptor mu 1 ( rs1799971) and inequity aversion. Regarding RS3, participants with the SS genotype had higher AIA than those with the SL or LL genotypes, but no association was found for DIA. Moreover, we observed no aversion associations for rs53576 or rs1799971. The results suggest that plays an important role in aversion when one's own gain is greater than that of others. Our findings may provide a solid theoretical basis for future studies on the relationship between genetic polymorphisms and inequity aversion.
Topics: Adult; Humans; Bayes Theorem; Receptors, Vasopressin; Genotype; Affect; Polymorphism, Genetic
PubMed: 37312550
DOI: 10.1098/rspb.2023.0378 -
Clinical Journal of the American... Apr 2022The vasopressin V2 receptor antagonist tolvaptan is the only drug that has been proven to be nephroprotective in autosomal dominant polycystic kidney disease (ADPKD).... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
The vasopressin V2 receptor antagonist tolvaptan is the only drug that has been proven to be nephroprotective in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan also causes polyuria, limiting tolerability. We hypothesized that cotreatment with hydrochlorothiazide or metformin may ameliorate this side effect.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We performed a clinical study and an animal study. In a randomized, controlled, double-blind, crossover trial, we included 13 tolvaptan-treated patients with ADPKD. Patients were treated for three 2-week periods with hydrochlorothiazide, metformin, or placebo in random order. Primary outcome was change in 24-hour urine volume. We also measured GFR and a range of metabolic and kidney injury markers.
RESULTS
Patients (age 45±8 years, 54% women, measured GFR of 55±11 ml/min per 1.73 m) had a baseline urine volume on tolvaptan of 6.9±1.4 L/24 h. Urine volume decreased to 5.1 L/24 h (<0.001) with hydrochlorothiazide and to 5.4 L/24 h (<0.001) on metformin. During hydrochlorothiazide treatment, plasma copeptin (surrogate for vasopressin) decreased, quality of life improved, and several markers of kidney damage and glucose metabolism improved. Metformin did not induce changes in these markers or in quality of life. Given these results, the effect of adding hydrochlorothiazide to tolvaptan was investigated on long-term kidney outcome in an animal experiment. Water intake in tolvaptan-hydrochlorothiazide cotreated mice was 35% lower than in mice treated with tolvaptan only. Combination treatment was superior to "no treatment" on markers of disease progression (kidney weight, =0.003 and cystic index, =0.04) and superior or equal to tolvaptan alone.
CONCLUSIONS
Both metformin and hydrochlorothiazide reduced tolvaptan-caused polyuria in a short-term study. Hydrochlorothiazide also reduced polyuria in a long-term animal model without negatively affecting nephroprotection.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_03_21_CJN11260821.mp3.
Topics: Adult; Animals; Antidiuretic Hormone Receptor Antagonists; Cross-Over Studies; Female; Humans; Hydrochlorothiazide; Kidney; Male; Metformin; Mice; Middle Aged; Polycystic Kidney, Autosomal Dominant; Polyuria; Quality of Life; Receptors, Vasopressin; Tolvaptan; Treatment Outcome
PubMed: 35314480
DOI: 10.2215/CJN.11260821 -
Structure (London, England : 1993) Nov 2023Arrestin-dependent G protein-coupled receptor (GPCR) signaling pathway is regulated by the phosphorylation state of GPCR's C-terminal domain, but the molecular bases of...
Arrestin-dependent G protein-coupled receptor (GPCR) signaling pathway is regulated by the phosphorylation state of GPCR's C-terminal domain, but the molecular bases of arrestin:receptor interaction are to be further illuminated. Here we investigated the impact of phosphorylation on the conformational features of the C-terminal region from three rhodopsin-like GPCRs, the vasopressin V2 receptor (V2R), the growth hormone secretagogue or ghrelin receptor type 1a (GHSR), and the β2-adernergic receptor (β2AR). Using phosphomimetic variants, we identified pre-formed secondary structure elements, or short linear motifs (SLiMs), that undergo specific conformational transitions upon phosphorylation. Of importance, such conformational transitions appear to favor arrestin-2 binding. Hence, our results suggest a model in which the phosphorylation-dependent structuration of the GPCR C-terminal regions would modulate arrestin binding and therefore signaling outcomes in arrestin-dependent pathways.
Topics: Arrestin; Phosphorylation; Receptors, G-Protein-Coupled; Signal Transduction; Rhodopsin
PubMed: 37669668
DOI: 10.1016/j.str.2023.08.011 -
Therapeutics and Clinical Risk... 2019Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and... (Review)
Review
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and increased kidney volume that eventually leads to end-stage renal disease. ADPKD is considered the fourth leading cause of end-stage renal disease in the United States and globally. Care of patients with ADPKD was, for a long time, limited to supportive lifestyle measures, due to the lack of therapeutic strategies targeting the main pathways involved in the pathophysiology of ADPKD. As the first FDA approved treatment of ADPKD, Vasopressin (V) receptor blocking agent, tolvaptan, is an urgently awaited advance for ADPKD patients. In our review, we also shed some lights on what is beyond Tolvaptan as there are other medications in the pipeline and many medications have been or are currently being studied in clinical trials such as Tesevatinib, Metformin and Pravastatin, with the goal of slowing the rate of progression of ADPKD by reducing the increase in total kidney volume or maintaining eGFR. Here, we review updates in the perspectives and management of ADPKD.
PubMed: 31692482
DOI: 10.2147/TCRM.S196244