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Genes, Brain, and Behavior Feb 2017We examined the extent to which the arginine vasopressin receptor 1a (AVPR1a) and dopamine receptor D4 (DRD4) were related to sensitive maternal behavior directly or...
We examined the extent to which the arginine vasopressin receptor 1a (AVPR1a) and dopamine receptor D4 (DRD4) were related to sensitive maternal behavior directly or indirectly via maternal social cognition. Participants were 207 (105 European-American and 102 African-American) mothers and their children (52% females). Sensitive maternal behavior was rated and aggregated across a series of tasks when infants were 6 months, 1 year and 2 years old. At 6 months, mothers were interviewed about their empathy, attributions about infant behavior and beliefs about crying to assess their parenting-related social cognition. Mothers with long alleles for AVPR1a and DRD4 engaged in more mother-oriented social cognition (i.e. negative attributions and beliefs about their infants' crying, β = 0.13, P < 0.05 and β = 0.16, P < 0.05, respectively), which in turn predicted less sensitive maternal behavior (β = -0.23, P < 0.01). Both indirect effects were statistically significant independent of one another and covariates [95% confidence interval (CI): -0.22, -0.03 and β = -0.03 for AVPR; 95% CI: -0.20, -0.03 and β = -0.04 for DRD4]. There were no significant direct effects of AVPR1a or DRD4 on maternal sensitivity (β = 0.02, P = .73 and β = -0.10, P = .57, respectively). The results did not vary for African-American and European-American mothers (Δχ = 18.76, Δdf = 16, P = 0.28). Results support the view that one mechanism by which maternal genes are associated with parental behavior is via social cognition.
Topics: Adult; Alleles; Arginine Vasopressin; Child, Preschool; Cognition; Female; Genetic Testing; Humans; Infant; Infant Behavior; Infant, Newborn; Male; Maternal Behavior; Mother-Child Relations; Polymorphism, Single Nucleotide; Receptors, Dopamine D4; Receptors, Vasopressin; Social Behavior; Stress, Psychological
PubMed: 27581946
DOI: 10.1111/gbb.12326 -
American Journal of Physiology. Renal... Nov 2018The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs)... (Review)
Review
The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI). A lack of VP production precipitates central diabetes insipidus (CDI), which can be managed effectively by VP supplementation. A majority of cases of nephrogenic diabetes insipidus (NDI) result from V2R mutations that impair receptor sensitivity. No specific therapy is currently available for management of NDI. Evidence is evolving that (pro)renin receptor (PRR), a newly identified member of the renin-angiotensin system, is capable of regulating VP production and action. As such, PRR should be considered strongly as a therapeutic target for treating CDI and NDI. The current review will summarize recent advances in understanding the physiology of renal and central PRR as it relates to the two types of DI.
Topics: Animals; Antidiuretic Agents; Diabetes Insipidus; Diuresis; Genetic Predisposition to Disease; Humans; Kidney; Mutation; Phenotype; Receptors, Cell Surface; Receptors, Vasopressin; Renin-Angiotensin System; Vasopressins; Prorenin Receptor
PubMed: 30019932
DOI: 10.1152/ajprenal.00266.2018 -
Best Practice & Research. Clinical... Mar 2016Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma... (Review)
Review
Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.
Topics: Animals; Aquaporin 2; Diabetes Insipidus, Nephrogenic; Genetic Diseases, X-Linked; Humans; Mutation; Receptors, Vasopressin
PubMed: 27156763
DOI: 10.1016/j.beem.2016.02.010 -
Scientific Reports Aug 2018The neurohormones arginine-vasopressin (AVP) and oxytocin (OT) synthesised in supraoptic and paraventricular nuclei of neurohypophysis regulate lactation, systemic water...
The neurohormones arginine-vasopressin (AVP) and oxytocin (OT) synthesised in supraoptic and paraventricular nuclei of neurohypophysis regulate lactation, systemic water homeostasis and nociception. Using transgenic rats expressing AVP and OT tagged with fluorescent proteins we demonstrate that both neurohormones are expressed in sensory neurones both in vitro, in primary cultures, and in situ, in the intact ganglia; this expression was further confirmed with immunocytochemistry. Both neurohormones were expressed in nociceptive neurones immunopositive to transient receptor potential vannilloid 1 (TRPV1) channel antibodies. The AVP and OT-expressing DRG neurones responded to AVP, OT, 50 mM K and capsaicin with [Ca] transients; responses to AVP and OT were specifically blocked by the antagonists of V AVP and OT receptors. Probing the extracellular incubation saline with ELISA revealed AVP and OT secretion from isolated DRGs; this secretion was inhibited by tetanus toxin (TeNT) indicating the role for vesicular release. Expression of OT, but not AVP in DRG neurones significantly increased during lactation. Together, the results indicate novel physiological roles (possibly related to nociception and mood regulation) of AVP and OT in the sensory neurones.
Topics: Animals; Dehydration; Exocytosis; Female; Fluorescence; Ganglia, Spinal; Lactation; Male; Nociception; Oxytocin; Pituitary Gland, Posterior; Rats, Transgenic; Receptors, Oxytocin; Receptors, Vasopressin; Sensory Receptor Cells; Vasopressins
PubMed: 30166555
DOI: 10.1038/s41598-018-31361-1 -
The Biochemical Journal Sep 2018A series of compounds formerly identified by high-throughput screening was studied for their ability to serve as pharmacoperones for the vasopressin type 2 receptor...
A series of compounds formerly identified by high-throughput screening was studied for their ability to serve as pharmacoperones for the vasopressin type 2 receptor (V2R) mutant L83Q, which is known to cause nephrogenic diabetes insipidus (NDI). Three compounds were particularly effective in rerouting the mutant receptor in a concentration-dependent manner, were neither agonists nor antagonists, and displayed low cellular toxicity. Compound 1 was most effective and can be used as a molecular probe for future studies of how small molecules may affect NDI caused by mutant V2R. These compounds, however, failed to rescue the V2R Y128S mutant, indicating that the compounds described may not work in the rescue of all known mutants of V2R. Taken collectively, the present studies have now identified a promising lead compound that could function as a pharmacoperone to correct the trafficking defect of the NDI-associated mutant V2R L83Q and thus has the therapeutic potential for the treatment of NDI.
Topics: Amino Acid Substitution; Diabetes Insipidus, Nephrogenic; HeLa Cells; Humans; Molecular Chaperones; Molecular Probes; Mutation, Missense; Receptors, Vasopressin
PubMed: 30068530
DOI: 10.1042/BCJ20180065 -
Journal of Agricultural and Food... Sep 2020Luteolin, a flavonoid widely distributed in the plant kingdom, contains two benzene rings and hydroxyl groups, and this structural specificity contributes to its diverse...
Luteolin, a flavonoid widely distributed in the plant kingdom, contains two benzene rings and hydroxyl groups, and this structural specificity contributes to its diverse biological activities. However, no previous studies have simultaneously investigated the therapeutic potency of luteolin isolated from a plant as an antipsychotic and antidepressant. Here, luteolin exhibited selective inhibition of hMAO-A (IC = 8.57 ± 0.47 μM) over hMAO-B (IC > 100 μM). proteochemometric modeling predicted promising targets of luteolin, and verification via cell-based G protein-coupled receptor functional assays showed that luteolin is a selective antagonist of the vasopressin receptor VR (IC = 19.49 ± 6.32 μM) and the dopamine D receptor (IC = 39.59 ± 1.46 μM). Molecular docking showed the tight binding of luteolin with a low binding score and the high stability of the luteolin-receptor complex, corroborating its functional effect. Thus, hMAO-A, hDR, and hVR are prime targets of luteolin and potential alternatives for the management of neurodegenerative diseases.
Topics: Antidiuretic Hormone Receptor Antagonists; Cirsium; Humans; Kinetics; Luteolin; Molecular Docking Simulation; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Plant Extracts; Receptors, Dopamine D4; Receptors, Vasopressin
PubMed: 32869630
DOI: 10.1021/acs.jafc.0c04502 -
ACS Chemical Neuroscience Aug 2018Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used... (Review)
Review
Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used laboratory mice and rats, Microtine rodents provide a unique model to study the neurobiology underlying pair bonding and the selective attachments that form between adults. Comparisons between monogamous prairie voles and the closely related but nonmonogamous meadow and montane voles have revealed that brain-region-specific neuropeptide receptor patterning modulates social behavior between and within species. In particular, diversity in vasopressin 1a receptor (V1aR) distribution has been linked to individual and species differences in monogamy-related behaviors such as partner preference, mate guarding, and space use. Given the importance of differential receptor expression for regulating social behavior, a critical question has emerged: What are the genetic and epigenetic mechanisms that underlie brain-region-specific receptor patterns? This review will summarize what is known about how the vasopressin (AVP)-V1aR axis regulates social behaviors via signaling in discrete brain regions. From this work, we propose that brain-region-specific regulatory mechanisms facilitate robust evolvability of V1aR expression to generate diverse sociobehavioral traits. Translationally, we provide a perspective on how these studies have contributed to our understanding of human social behaviors and how brain-region-specific regulatory mechanisms might be harnessed for targeted therapies to treat social deficits in psychiatric disorders such as depression, complicated grief, and autism spectrum disorder.
Topics: Animals; Arvicolinae; Brain; Epigenesis, Genetic; Humans; Models, Animal; Object Attachment; Pair Bond; Receptors, Vasopressin; Species Specificity
PubMed: 29513516
DOI: 10.1021/acschemneuro.7b00475 -
International Journal of Molecular... Nov 2021Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in... (Review)
Review
Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules. Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. Dysregulation of AQP2 is also a cause of water retention with hyponatremia in heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone vasopressin is an upstream regulator of AQP2. Its binding to the vasopressin V2 receptor promotes AQP2 targeting to the apical membrane and thus enables water reabsorption. Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia. However, there are no studies showing improvement in hard outcomes or long-term prognosis. A possible reason is that vasopressin receptors have many downstream effects other than AQP2 function. It is expected that the development of drugs that directly target AQP2 may result in increased treatment specificity and effectiveness for water balance disorders. This review summarizes recent progress in studies of AQP2 and drug development challenges for water balance disorders.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Body Water; Calcium Signaling; Cytoskeleton; Diabetes Insipidus, Nephrogenic; Endocytosis; Humans; Kidney Tubules, Collecting; Loss of Function Mutation; Molecular Targeted Therapy; Osmolar Concentration; Phosphorylation; Protein Transport; Receptors, Vasopressin; Water-Electrolyte Balance
PubMed: 34884753
DOI: 10.3390/ijms222312950 -
The Journal of Pharmacology and... May 2020It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles...
It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Arginine Vasopressin; Benzazepines; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases; Dogs; Ear, Inner; Female; Male; Motion Sickness; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Signal Transduction
PubMed: 32165443
DOI: 10.1124/jpet.119.264390 -
General and Comparative Endocrinology Sep 2020Myopathies (Woody Breast (WB) and White Striping (WS)) of broiler chickens have been correlated with fast growth. Recent studies reported that localized hypoxia and...
Myopathies (Woody Breast (WB) and White Striping (WS)) of broiler chickens have been correlated with fast growth. Recent studies reported that localized hypoxia and metabolic impairment may involve in these myopathies of birds. In order to better understand the stress response mechanisms affecting myopathies of broilers, the aim of this study was to examine effects of WB and both WB/WS on stress hormone corticosterone (CORT) levels and expressional changes of stress response genes including glucocorticoid (GC) receptor (GR), 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), DNA methylation regulators (DNMTs), and arginine vasotocin receptor 1a and 1b (V1aR, V1bR). Results of radioimmunoassay showed that CORT levels of WB and WB/WS birds were significantly higher compared to Con (p < 0.05), however, the combination of WB/WS was not significantly higher than WB birds, implying that the effects of WB and WS on CORT are not synergistic. Hepatic GR expression of both WB and WB/WS birds were significantly higher compared to Con (p < 0.05). However, GR expression levels in breast muscle of both WB and WB/WS birds were decreased compared to Con (p < 0.05). Hepatic 11β-HSD1 expression was increased only in WB/WS birds compared to Con birds with no significant difference between Con and WB birds. 11β-HSD1 expression was decreased and increased in WB and WB/WS birds compared to Con, respectively, in breast muscle (p < 0.05). DNMT1 expression was significantly decreased in both muscle and liver of WB birds, and in muscle of WB/WS birds, but not in liver of WB/WS birds, indicating differential effects of WS on the epigenetical stress response of muscle and liver compared to WB. V1aR expression was significantly increased in muscle of WB birds, and in liver of WB/WS birds compared to Con birds (p < 0.05). V1bR was not changed in muscle and liver of WB birds compared to Con birds. Taken together, results suggest that GC-induced myopathies occur in fast-growing broiler chickens and circulating CORT level might be a significant biochemical marker of myopathies (WB and WS) of birds. In addition, chronic stress responses in breast muscle and tissue-specific epigenetic changes of stress response genes by DNMTs may play a critical role in the occurrence of myopathies.
Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Animals; Body Weight; Chickens; Corticosterone; DNA Methylation; Female; Gene Expression Regulation, Developmental; Liver; Mammary Glands, Animal; Muscles; Muscular Diseases; Organ Specificity; Receptors, Glucocorticoid; Receptors, Vasopressin; Stress, Physiological
PubMed: 32540490
DOI: 10.1016/j.ygcen.2020.113526