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International Journal of Molecular... Mar 2020Oxytocin (OT)/vasopressin (VP) signaling system is important to the regulation of metabolism, osmoregulation, social behaviours, learning, and memory, while the...
Oxytocin (OT)/vasopressin (VP) signaling system is important to the regulation of metabolism, osmoregulation, social behaviours, learning, and memory, while the regulatory mechanism on ovarian development is still unclear in invertebrates. In this study, ot/vp-like and its receptor (ot/vpr-like) were identified in the mud crab Scylla paramamosain. ot/vp-like transcripts were mainly expressed in the nervous tissues, midgut, gill, hepatopancreas, and ovary, while ot/vpr-like were widespread in various tissues including the hepatopancreas, ovary, and hemocytes. In situ hybridisation revealed that ot/vp-like mRNA was mainly detected in 6-9 clusters in the cerebral ganglion, and oocytes and follicular cells in the ovary, while ot/vpr-like was found to localise in F-cells in the hepatopancreas and oocytes in the ovary. In vitro experiment showed that the mRNA expression level of vg in the hepatopancreas, vgr in the ovary, and 17β-estradiol (E) content in culture medium were significantly declined with the administration of synthetic OT/VP-like peptide. Besides, after the injection of OT/VP-like peptide, it led to the significantly reduced expression of vg in the hepatopancreas and subduced E content in the haemolymph in the crabs. In brief, OT/VP signaling system might inhibit vitellogenesis through neuroendocrine and autocrine/paracrine modes, which may be realised by inhibiting the release of E.
Topics: Animals; Brachyura; Female; Ganglia, Invertebrate; Hepatopancreas; Ovary; Oxytocin; Receptors, Oxytocin; Receptors, Vasopressin; Transcriptome; Vasopressins; Vitellogenesis
PubMed: 32225106
DOI: 10.3390/ijms21072297 -
Kidney International Nov 2009[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels... (Review)
Review
[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, V1aR(-/-) mice exhibited (1) blunted AVP-induced vasopressor response, (2) impaired arterial baroreceptor reflex, (3) decreased sympathetic nerve activity, and (4) decreased blood volume, all of which could contribute to the observed hypotension. In relation to their decreased blood volume, V1aR(-/-) mice had decreased plasma aldosterone levels, which could result not only from decreased activity of the renin-angiotensin system (RAS), but also from impaired AVP-stimulated aldosterone release in the adrenal glands. V1aR was found to specifically co-express at the macula densa cells with cyclooxygenase (COX)-2 and with neuronal nitric oxide synthase, which produces potent stimulators of renin, PGE(2), and NO. The expression levels of renin, COX-2, and nNOS were significantly decreased in V1aR(-/-) mice, which led to the suppression of RAS activity and consequent decreases in aldosterone and blood volume. Furthermore, V1aR is also expressed in collecting duct cells and involved in regulating water reabsorption by affecting V2/aquaporin 2 function. Thus, AVP regulates blood pressure and volume via V1aR by exerting diverse functions in vivo.
Topics: Animals; Arginine Vasopressin; Blood Pressure; Blood Volume; Mice; Mice, Knockout; Models, Biological; Receptors, Vasopressin; Renin-Angiotensin System; Vasoconstrictor Agents
PubMed: 19693000
DOI: 10.1038/ki.2009.319 -
The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors.American Journal of Physiology. Renal... May 2014The arginine vasopressin (AVP) type 2 receptor (V2R) is unique among AVP receptor subtypes in signaling through cAMP. Its key function is in the kidneys, facilitating... (Review)
Review
The arginine vasopressin (AVP) type 2 receptor (V2R) is unique among AVP receptor subtypes in signaling through cAMP. Its key function is in the kidneys, facilitating the urine concentrating mechanism through the AVP/V2 type receptor/aquaporin 2 system in the medullary and cortical collecting ducts. Recent clinical and research observations strongly support the existence of an extrarenal V2R. The clinical importance of the extrarenal V2R spans widely from stimulation of coagulation factor in the endothelium to as yet untested potential therapeutic targets. These include V2R-regulated membranous fluid turnover in the inner ear, V2R-regulated mitogensis and apoptosis in certain tumor tissues, and numerous other cell types where the physiological role of V2Rs still requires further research. Here, we review current evidence on the physiological and pathophysiological functions of renal and extrarenal V2Rs. These functions of V2R are important, not only in rare diseases with loss or gain of function of V2R but also in relation to the recent use of nonpeptide V2R antagonists to treat hyponatremia and possibly retard the growth of cysts and development of renal failure in autosomal dominant polycystic kidney disease. The main functions of V2R in principal cells of the collecting duct are water, salt, and urea transport by modifying the trafficking of aquaporin 2, epithelial Na(+) channels, and urea transporters and vasodilation and stimulation of coagulation factor properties, mainly seen with pharmacological doses of 1-desamino-8-D-AVP. The AVPR2 gene is located on the X chromosome, in a region with high probability of escape from inactivation; this may lead to phenotypic sex differences, with females expressing higher levels of transcript than males.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Cyclic AMP; Female; Gene Expression Regulation; Genotype; Hormone Antagonists; Humans; Kidney; Male; Phenotype; Receptors, Vasopressin; Signal Transduction; Vasopressins; Water-Electrolyte Balance
PubMed: 24598801
DOI: 10.1152/ajprenal.00604.2013 -
Annual Review of Pharmacology and... Jan 2022Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the... (Review)
Review
Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing-based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailedframework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia.
Topics: Aquaporin 2; Bayes Theorem; Humans; Receptors, Vasopressin; Systems Biology; Water-Electrolyte Imbalance
PubMed: 34579536
DOI: 10.1146/annurev-pharmtox-052120-011012 -
Neuromodulation : Journal of the... Jul 2016The study aims to know the effect of electroacupuncture (EA) in maintenance of the homeostasis of the neuroendocrine system in hepatectomy rats and the involvement of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The study aims to know the effect of electroacupuncture (EA) in maintenance of the homeostasis of the neuroendocrine system in hepatectomy rats and the involvement of arginine vasopressin (AVP) signaling in hypothalamus after EA was observed.
MATERIALS AND METHODS
Rats were randomly assigned to four groups, including the intact group, model group, sham-EA group, and EA group. EA was given during the perioperative period at the Zusanli (ST36) and Sanyinjiao (SP6) points after hepatectomy. The serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were detected via radioimmunoassay. The expression of AVP, arginine vasopressin receptor 1a (AVPR1a), arginine vasopressin receptor 1b (AVPR1b), and glucocorticoid receptor (GR) was detected by Western blot after surgery.
RESULTS
Compared with the intact group, the ACTH and CORT levels in the serum of model group were increased, whereas the ACTH and CORT levels were decreased in the EA group compared with the model group. Moreover, AVP and AVPR1b protein levels in the pituitary gland were increased in the model group and decreased in the EA group. Further, a distinct increase in the AVP and AVPR1a protein levels was observed in the model group, whereas they were significantly decreased in the EA group. Blockade of AVPR1b by nelivaptan reduced the increase of ACTH and CORT. D [Leu(4) , Lys(8) ] vasopressin can inhibit the effect of EA in rectification of the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis.
CONCLUSIONS
EA application at ST36 and SP6 can ameliorate the hyperactivity of the HPA axis via AVP signaling during the perioperative period.
Topics: Acupuncture Points; Adrenocorticotropic Hormone; Analysis of Variance; Animals; Arginine Vasopressin; Corticosterone; Disease Models, Animal; Electroacupuncture; Gene Expression Regulation; Hepatectomy; Hyperkinesis; Hypothalamo-Hypophyseal System; Mice; Neuropeptides; RNA, Messenger; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid; Receptors, Vasopressin; Signal Transduction
PubMed: 26573696
DOI: 10.1111/ner.12366 -
Brain Structure & Function Mar 2023The nonapeptide system modulates numerous social behaviors through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1A)...
The nonapeptide system modulates numerous social behaviors through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1A) in the brain. OXTRs and AVPR1As are widely distributed throughout the brain and binding densities exhibit substantial variation within and across species. Although OXTR and AVPR1A binding distributions have been mapped for several rodents, this system has yet to be characterized in the spiny mouse (Acomys cahirinus). Here we conducted receptor autoradiography and in situ hybridization to map distributions of OXTR and AVPR1A binding and Oxtr and Avpr1a mRNA expression throughout the basal forebrain and midbrain of male and female spiny mice. We found that nonapeptide receptor mRNA is diffuse throughout the forebrain and midbrain and does not always align with OXTR and AVPR1A binding. Analyses of sex differences in brain regions involved in social behavior and reward revealed that males exhibit higher OXTR binding densities in the lateral septum, bed nucleus of the stria terminalis, and anterior hypothalamus. However, no association with gonadal sex was observed for AVPR1A binding. Hierarchical clustering analysis further revealed that co-expression patterns of OXTR and AVPR1A binding across brain regions involved in social behavior and reward differ between males and females. These findings provide mapping distributions and sex differences in nonapeptide receptors in spiny mice. Spiny mice are an excellent organism for studying grouping behaviors such as cooperation and prosociality, and the nonapeptide receptor mapping here can inform the study of nonapeptide-mediated behavior in a highly social, large group-living rodent.
Topics: Animals; Female; Male; Receptors, Oxytocin; RNA, Messenger; Basal Forebrain; Mesencephalon; Oxytocin; Receptors, Vasopressin; Vasopressins; Social Behavior; Murinae
PubMed: 36271259
DOI: 10.1007/s00429-022-02581-z -
Journal of Pharmacological Sciences 2014Arginine vasopressin (AVP) is a 9-amino acid peptide that is secreted from the posterior pituitary in response to high plasma osmolality and hypotension. AVP has... (Review)
Review
Arginine vasopressin (AVP) is a 9-amino acid peptide that is secreted from the posterior pituitary in response to high plasma osmolality and hypotension. AVP has important roles in circulatory and water homoeostasis, which are mediated by oxytocin receptors and by AVP receptor subtypes: V(1a) (mainly vascular), V(1b) (pituitary), and V(2) (renal). Vaptans are orally and intravenously active nonpeptide vasopressin-receptor antagonists. Recently, subtype-selective nonpeptide vasopressin-receptor agonists have been developed. A selective V(1a)-receptor antagonist, relcovaptan, has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhea, and tocolysis. A selective V(1b)-receptor antagonist, nelivaptan, has beneficial effects in the treatment of psychiatric disorders. Selective V2-receptor antagonists including mozavaptan, lixivaptan, satavaptan, and tolvaptan induce highly hypotonic diuresis without substantially affecting the excretion of electrolytes. A nonselective V(1a)/V(2)-receptor antagonist, conivaptan, is used in the treatment for euvolaemic or hypervolemic hyponatremia. Recent basic and clinical studies have shown that AVP-receptor antagonists, especially V2-receptor antagonists, may have therapeutic potential for heart failure. This review presents current information about AVP and its antagonists.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Benzamides; Benzazepines; Body Water; Clinical Trials as Topic; Disease Models, Animal; Heart Failure; Homeostasis; Humans; Hyponatremia; Morpholines; Pyrroles; Receptors, Vasopressin; Spiro Compounds; Tolvaptan; Ventricular Remodeling
PubMed: 24401675
DOI: 10.1254/jphs.13r13cp -
PloS One 2017Pharmacoperones are small molecules that diffuse into cells and rescue misfolded, mistrafficked protein mutants, restoring their function. These substances act with high...
Pharmacoperones are small molecules that diffuse into cells and rescue misfolded, mistrafficked protein mutants, restoring their function. These substances act with high target specificity, serving as templates to fold (or refold) receptors, enzymes, ion channels or other proteins and enable them to pass the scrutiny of the cellular quality control system ("rescue"). In the present study we demonstrate that a rescued mutant (L83Q) of the vasopressin type 2 receptor (V2R), shows a strong bias for Gs coupling unlike the WT V2 receptor, which couples to both Gs and Gq/11. Failure of the mutant to couple to Gq/11 was not due to a limiting quantity of G-proteins since other Gq/11-coupled receptors (WT V2R, histamine receptor and muscarinic receptor) responded appropriately to their ligands. Transfection with DNA encoding Gq enabled the V2 receptor mutant to couple to this G protein, but only modestly compared with the WT receptor. Fourteen V2R mutant pharmacoperones, of multiple chemical classes, obtained from a high throughput screen of a 660,000 structure library, and one V2R peptidomimetic antagonist rescues L83Q. The rescued mutant shows similar bias with all pharmacoperones identified, suggesting that the bias is intrinsic to the mutant protein's structure, rather than due to the chemical class of the pharmacoperone. In the case of V2R mutant Y128S, rescue with a pharmacoperone revealed constitutive activity, also with bias for Gs, although both IP and cAMP were produced in response to agonist. These results suggest that particular rescued receptor mutants show functional characteristics that differ from the WT receptor; a finding that may be important to consider as pharmacoperones are developed as therapeutic agents.
Topics: Antidiuretic Hormone Receptor Antagonists; Cyclic AMP; GTP-Binding Protein alpha Subunits, Gq-G11; HeLa Cells; High-Throughput Screening Assays; Humans; Models, Molecular; Morpholines; Mutation; Receptors, Vasopressin; Small Molecule Libraries; Spiro Compounds
PubMed: 28767678
DOI: 10.1371/journal.pone.0181830 -
Neuron Mar 2010Human beings are an incredibly social species and along with eusocial insects engage in the largest cooperative living groups in the planet's history. Twin and family... (Review)
Review
Human beings are an incredibly social species and along with eusocial insects engage in the largest cooperative living groups in the planet's history. Twin and family studies suggest that uniquely human characteristics such as empathy, altruism, sense of equity, love, trust, music, economic behavior, and even politics are partially hardwired. The leap from twin studies to identifying specific genes engaging the social brain has occurred in the past decade, aided by deep insights accumulated about social behavior in lower mammals. Remarkably, genes such as the arginine vasopressin receptor and the oxytocin receptor contribute to social behavior in a broad range of species from voles to man. Other polymorphic genes constituting the "usual suspects"--i.e., those encoding for dopamine reward pathways, serotonergic emotional regulation, or sex hormones--further enable elaborate social behaviors.
Topics: Altruism; Animals; Choice Behavior; Games, Experimental; Genetic Phenomena; Humans; Receptors, Vasopressin; Social Behavior; Social Perception; Species Specificity; Twins
PubMed: 20346758
DOI: 10.1016/j.neuron.2010.02.020 -
Journal of Neuroendocrinology Jul 2023Parenting induces many neurological and behavioral changes that enable parents to rear offspring. Vasopressin plays an important role in this process via its effects on...
Parenting induces many neurological and behavioral changes that enable parents to rear offspring. Vasopressin plays an important role in this process via its effects on cognition, affect, and neuroplasticity, and in some cases, via interactions with decreased parental androgens. Thus far, the role of these hormones has been primarily studied in rodents. To address this gap, we explored vasopressin receptors and androgens in titi monkeys, a pair-bonding and biparental primate species. In Studies 1 and 2, we used receptor autoradiography to correlate arginine vasopressin receptor 1a (AVPR1a) binding in the hippocampus (Study 1, n = 10) and the rest of the forebrain (Study 2, n = 23) with parental status, parental experience, parity, infant carrying, and pair affiliation. We found that parents exhibited lower AVPR1a binding than non-parents throughout most brain regions assessed, with especially strong effects in the hippocampus (β = -.61), superior colliculus (β = -.88), lateral septum (β = -.35), and medial preoptic area (β = -.29). The other measures of parental experience also tended to be negatively associated with AVPR1a binding across different brain regions. In Study 3 (n = 44), we compared pre- and postpartum urinary androgen levels in parents and non-parents and found that mothers exhibited a sustained androgen decrease across 3-4 months postpartum (relative to 3 months prepartum; β ranged from -.72 to -.62 for different comparisons). For males, we found that multiparous fathers exhibited decreased androgen levels at 1-2 weeks postpartum (β = -.25) and at 3-4 months postpartum (β = -.40) compared to the prepartum, indicating both immediate and long-term reductions with subsequent paternal experience. Together, the results of this study suggest that decreases in AVPR1a binding and circulating androgens are associated with parental behavior and physiology in titi monkeys.
Topics: Male; Humans; Animals; Pregnancy; Female; Receptors, Vasopressin; Androgens; Callicebus; Brain; Postpartum Period
PubMed: 37267441
DOI: 10.1111/jne.13304