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Peptides Jul 2024Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus... (Review)
Review
Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus (SCN), the center of the circadian clock in mammals, is composed of multiple cell types that form a network that provides the basis for the remarkable stability of the circadian clock. Among the neuropeptides expressed in the SCN, arginine vasopressin (AVP) has attracted much attention because of its deep involvement in the function of circadian rhythms, as elucidated in particular by studies using genetically engineered mice. This review briefly summarizes the current knowledge on the peptidergic distribution and topographic neuronal organization in the SCN, the molecular mechanisms of the clock genes, and the relationship between the SCN and peripheral clocks. With respect to the physiological roles of AVP and AVP-expressing neurons, in addition to a sex-dependent action of AVP in the SCN, studies using AVP receptor knockout mice and mice genetically manipulated to alter the clock properties of AVP neurons are summarized here, highlighting its importance in maintaining circadian homeostasis and its potential as a target for therapeutic interventions.
Topics: Animals; Arginine Vasopressin; Suprachiasmatic Nucleus; Homeostasis; Circadian Rhythm; Humans; Mice; Circadian Clocks; Neurons; Mice, Knockout; Receptors, Vasopressin
PubMed: 38663583
DOI: 10.1016/j.peptides.2024.171229 -
Life Science Alliance Aug 2024It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs)...
It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs) heteromerize with α-adrenoceptors (α-ARs) through which CRs are regulated. Here, we show that arginine vasopressin receptor 1A (AVPR1A) heteromerizes with all human CRs, except chemokine (C-X-C motif) receptor (CXCR)1, in recombinant systems and that such heteromers are detectable in THP-1 cells and human monocytes. We demonstrate that ligand-free AVPR1A differentially regulates the efficacy of CR partners to mediate chemotaxis and that AVPR1A ligands disrupt AVPR1A:CR heteromers, which enhances chemokine (C-C motif) receptor (CCR)1-mediated chemotaxis and inhibits CCR2-, CCR8-, and CXCR4-mediated chemotaxis. Using bioluminescence resonance energy transfer to monitor G protein activation and CRISPR/Cas9 gene-edited THP-1 cells lacking AVPR1A or α-AR, we show that CRs that share the propensity to heteromerize with α-ARs and AVPR1A exist and function within interdependent hetero-oligomeric complexes through which the efficacy of CRs to mediate chemotaxis is controlled. Our findings suggest that hetero-oligomers composed of CRs, α-ARs, and AVPR1A may enable stress hormones to regulate immune cell trafficking.
Topics: Humans; Monocytes; Chemotaxis; Receptors, Chemokine; Receptors, Vasopressin; THP-1 Cells; Protein Multimerization; HEK293 Cells; Receptors, CXCR4; CRISPR-Cas Systems; Signal Transduction; Receptors, Adrenergic, alpha-1; Ligands
PubMed: 38782603
DOI: 10.26508/lsa.202402657 -
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 -
International Journal of Molecular... Sep 2023Autosomal-Dominant Polycystic Kidney Disease (ADPKD) is a monogenic disorder initiated by mutations in either or genes, responsible for encoding polycystin 1 and... (Review)
Review
Autosomal-Dominant Polycystic Kidney Disease (ADPKD) is a monogenic disorder initiated by mutations in either or genes, responsible for encoding polycystin 1 and polycystin 2, respectively. These proteins are primarily located within the primary cilia. The disease follows an inexorable progression, leading most patients to severe renal failure around the age of 50, and extra-renal complications are frequent. A cure for ADPKD remains elusive, but some measures can be employed to manage symptoms and slow cyst growth. Tolvaptan, a vasopressin V2 receptor antagonist, is the only drug that has been proven to attenuate ADPKD progression. Recently, autophagy, a cellular recycling system that facilitates the breakdown and reuse of aged or damaged cellular components, has emerged as a potential contributor to the pathogenesis of ADPKD. However, the precise role of autophagy in ADPKD remains a subject of investigation, displaying a potentially twofold impact. On the one hand, impaired autophagy may promote cyst formation by inducing apoptosis, while on the other hand, excessive autophagy may lead to fibrosis through epithelial to mesenchymal transition. Promising results of autophagy inducers have been observed in preclinical studies. Clinical trials are warranted to thoroughly assess the long-term safety and efficacy of a combination of autophagy inducers with metabolic and/or aquaferetic drugs. This research aims to shed light on the complex involvement of autophagy in ADPKD, explore the regulation of autophagy in disease progression, and highlight the potential of combination therapies as a promising avenue for future investigations.
Topics: Humans; Aged; Polycystic Kidney, Autosomal Dominant; Epithelial-Mesenchymal Transition; Kidney; Autophagy; Cysts
PubMed: 37834113
DOI: 10.3390/ijms241914666 -
Nature Reviews. Endocrinology May 2024Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes... (Review)
Review
Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific for AVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.
PubMed: 38693275
DOI: 10.1038/s41574-024-00985-x -
British Journal of Clinical Pharmacology Mar 2024Although diuretics play an important role in triple-whammy acute kidney injury (AKI), it is unclear whether the type of diuretic influences the risk of triple-whammy...
Although diuretics play an important role in triple-whammy acute kidney injury (AKI), it is unclear whether the type of diuretic influences the risk of triple-whammy AKI. The aim of this study was to evaluate whether vasopressin receptor antagonists affect triple-whammy AKI. This cross-sectional study used disproportionality analysis of VigiBase data to assess the risk of AKI with various diuretics. Although multiple logistic regression analysis showed that aldosterone antagonists (odds ratio [OR] 2.19, 95% CI 2.01-2.37), loop diuretics (OR 4.40, 95% CI 4.07-4.76) and thiazide diuretics (OR 1.98, 95% CI 1.83-2.15) increased the risk of AKI in patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and renin-angiotensin system inhibitors (RASi), vasopressin receptor antagonists did not increase the risk of AKI in those patients. Vasopressin receptor antagonists might not influence the development of triple-whammy AKI.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Antidiuretic Hormone Receptor Antagonists; Cross-Sectional Studies; Angiotensin Receptor Antagonists; Anti-Inflammatory Agents, Non-Steroidal; Diuretics; Acute Kidney Injury
PubMed: 37990649
DOI: 10.1111/bcp.15974 -
International Journal of Molecular... Jan 2024The present review draws attention to the specific role of angiotensin peptides [angiotensin II (Ang II), angiotensin-(1-7) (Ang-(1-7)], vasopressin (AVP), and insulin... (Review)
Review
The present review draws attention to the specific role of angiotensin peptides [angiotensin II (Ang II), angiotensin-(1-7) (Ang-(1-7)], vasopressin (AVP), and insulin in the regulation of the coronary blood flow and cardiac contractions. The interactions of angiotensin peptides, AVP, and insulin in the heart and in the brain are also discussed. The intracardiac production and the supply of angiotensin peptides and AVP from the systemic circulation enable their easy access to the coronary vessels and the cardiomyocytes. Coronary vessels and cardiomyocytes are furnished with AT1 receptors, AT2 receptors, Ang (1-7) receptors, vasopressin V1 receptors, and insulin receptor substrates. The presence of some of these molecules in the same cells creates good conditions for their interaction at the signaling level. The broad spectrum of actions allows for the engagement of angiotensin peptides, AVP, and insulin in the regulation of the most vital cardiac processes, including (1) cardiac tissue oxygenation, energy production, and metabolism; (2) the generation of the other cardiovascular compounds, such as nitric oxide, bradykinin (Bk), and endothelin; and (3) the regulation of cardiac work by the autonomic nervous system and the cardiovascular neurons of the brain. Multiple experimental studies and clinical observations show that the interactions of Ang II, Ang(1-7), AVP, and insulin in the heart and in the brain are markedly altered during heart failure, hypertension, obesity, and diabetes mellitus, especially when these diseases coexist. A survey of the literature presented in the review provides evidence for the belief that very individualized treatment, including interactions of angiotensins and vasopressin with insulin, should be applied in patients suffering from both the cardiovascular and metabolic diseases.
Topics: Humans; Angiotensin II; Arginine Vasopressin; Diabetes Mellitus; Insulin; Obesity; Receptors, Angiotensin; Receptors, Vasopressin; Vasopressins
PubMed: 38279313
DOI: 10.3390/ijms25021310 -
Naunyn-Schmiedeberg's Archives of... Nov 2023Although studies suggest that cognitive functions in the elderly are impaired, elderly people tend to be more successful and wiser in solving emotional problems. In...
Although studies suggest that cognitive functions in the elderly are impaired, elderly people tend to be more successful and wiser in solving emotional problems. In empathy-like behavior models, the observer rat rescues the distressed cage mate by displaying emotional and cognitive ability. The aim of the study was to investigate the changes in empathy-like behavior in older rats in comparison to adult rats. In addition, we wanted to determine the effects of alterations in neurochemicals (such as corticosterone, oxytocin, vasopressin, and their receptor levels) and emotional situations on this behavior. In our study, we initially completed empathy-like behavior tests and emotional tests (open field, elevated plus maze) and performed neurochemical examinations in the serum and brain tissues. In the second step of research, we applied a midazolam (benzodiazepine) treatment to examine the effect of anxiety on empathy-like behavior. In the old rats, we observed that empathy-like behavior deteriorated, and anxiety signs were more pronounced. We detected a positive correlation between the latency in empathy-like behavior and corticosterone levels and v1b receptor levels. The midazolam effect on empathy-like behavior was attenuated by flumazenil (a benzodiazepine receptor antagonist). The recordings of ultrasonic vocalization showed frequencies around 50 kHz emitted by the observer and this was associated with the expectation of social contact. Our results state that compared to adult rats, old rats were more concerned and failed during empathy-like behavior. Midazolam may improve this behavior by anxiolysis.
Topics: Humans; Rats; Animals; Aged; Midazolam; Anti-Anxiety Agents; Empathy; Corticosterone; Anxiety; Behavior, Animal
PubMed: 37209151
DOI: 10.1007/s00210-023-02526-1 -
Journal of Personalized Medicine Feb 2024Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during... (Review)
Review
Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted in this review. When discussing what new therapeutic agent might be an alternative to hormone therapy and menopause replacement therapy for migraine treatment, the panel pointed to oxytocin delivered as a nasal spray. Overall, the conclusion was that progress in the preclinical study of hormones on the nervous system has been challenging and slow, that there remain substantial gaps in our understanding of the complex roles sex hormones play in migraine, and that opportunities remain for improved or novel therapeutic agents. Manipulation of sex hormones, perhaps through biochemical modifications where its positive effects are selected for and side effects are minimized, remains a theoretical goal, one that might have an impact on migraine disease and other symptoms of menopause. This review is a call to action for increased interest and funding for preclinical research on sex hormones, their metabolites, and their receptors. Interdisciplinary research, perhaps facilitated by a collaborative communication network or panel, is a possible strategy to achieve this goal.
PubMed: 38392617
DOI: 10.3390/jpm14020184 -
Biomedicine & Pharmacotherapy =... Sep 2023The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites....
Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites.
The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration-response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205's lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.
Topics: Rats; Animals; Diuretics; Natriuretic Agents; Ascites; Vasopressins; Liver Cirrhosis; Sodium; Receptors, Vasopressin; Hypertension, Portal; Hyperaldosteronism
PubMed: 37418980
DOI: 10.1016/j.biopha.2023.115116