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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 -
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 -
Current Research in Physiology 2022The mechanisms involved in urinary bladder control are not fully understood, but it is well accepted that a complex central network is involved in micturition control....
The mechanisms involved in urinary bladder control are not fully understood, but it is well accepted that a complex central network is involved in micturition control. The micturition reflex can be modulated by direct cortical influence through facilitatory and inhibitory mechanisms. In addition, humoral mechanisms are involved in the bladder control. Vasopressin increases bladder contraction and intravesical pressure. This study sought to investigate the effect of intravenous injections of vasopressin receptor antagonists on cystometric parameters in anesthetized female rats. Isoflurane anesthetized adult female Wistar rats underwent femoral artery and vein cannulation for arterial pressure (AP) and heart rate (HR) recordings, and infusion of drugs, respectively. The bladder was also cannulated for intravesical pressure (IP) recordings and infusion of saline (10 mL/h) for cystometric evaluation. After baseline AP, HR and IP recordings, saline (vehicle, 1 mL/kg), V1a (5 μg/kg) or V2 receptor antagonist (5 μg/kg) was injected i.v. and after 25 min the cystometry was carried out. Neither saline nor V1a or V2 receptor blockade evoked any change in AP, HR and IP. Nevertheless, during cystometry, the threshold pressure of the micturition reflex was significantly reduced in rats with V1a (to 19.30 ± 2.39 mmHg) and V2 receptor blockade (to 19.88 ± 2.49 mmHg) compared to the saline group (28.85 ± 2.06 mmHg, p = 0.014). No difference was observed in the other cystometric parameters. Therefore, the data suggest that blockade of V1a and V2 receptors reduces the threshold pressure of the micturition reflex and does not influence other cystometric parameters in anesthetized female Wistar rats.
PubMed: 36193514
DOI: 10.1016/j.crphys.2022.09.004 -
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 -
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 -
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 -
Journal of Experimental Pharmacology 2018Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V) receptors, is a pro-drug for the endogenous/natural porcine hormone...
Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg]-vasopressin (AVP) at V and vasopressin-2 (V) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V and V receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V) and cyclic adenosine monophosphate (V). Binding potency at V and V was AVP>LVP>>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V than for V. Cellular activity potency was also AVP>LVP>>terlipressin. Terlipressin was a partial agonist at V and a full agonist at V; LVP was a full agonist at both V and V. The in vivo response to terlipressin is likely due to the partial V agonist activity of terlipressin and full V agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.
PubMed: 29302194
DOI: 10.2147/JEP.S146034 -
Biochemical and Biophysical Research... Nov 2023Many insects produce the cyclic neuropeptide inotocin (CLITNCPRGamide), which is the insect orthologue of the mammalian neuropeptides oxytocin and vasopressin. These...
Many insects produce the cyclic neuropeptide inotocin (CLITNCPRGamide), which is the insect orthologue of the mammalian neuropeptides oxytocin and vasopressin. These insects also have one inotocin G protein-coupled receptor (GPCR), which is the orthologue of the mammalian oxytocin and vasopressin receptors. The tick Ixodes scapularis belongs to the subphylum Chelicerata, an arthropod taxon different from insects, to which also spiders, scorpions, and mites belong. I. scapularis is an ectoparasite and a health risk for humans, because it transfers pathogenic microorganisms to its human host during a blood meal, thereby causing serious neurological diseases, among them Lyme disease and tick-borne encephalitis (TBE). By annotating the genomic sequence of I. scapularis, we previously found one presumed tick inotocin preprohormone gene and, in contrast to insects, three genes coding for presumed inotocin GPCRs. We now find that these GPCR genes cluster on one genomic contig, suggesting that they originated by recent gene duplications. Closely located on the same contig are also four adipokinetic hormone/corazonin-related peptide (ACP) GPCR genes, and one crustacean cardioactive peptide (CCAP) GPCR gene, suggesting evolutionary relationships. These evolutionary relationships are confirmed by phylogenetic tree analyses of their gene products. We also cloned the tick inotocin preprohormone, which has a structural organization closely resembling mammalian oxytocin and vasopressin preprohormones, including the presence of a conserved neurophysin sequence, having seven cystine bridges. This neurophysin sequence has two cystine-knot domains, but in contrast to mammalian neurophysins, the tick neurophysin contains a canonical prohormone convertase cleavage signal and a peptide C-terminal amidation sequence (GKR), suggesting cleavage into two biologically active cystine-knot peptides. This cleavage/amidation sequence occurs in neurophysins from most hard tick species, but not in other chelicerates. Mature tick inotocin is different from insect inotocin and has the sequence CFITNCPPGamide. Finally, we cloned and stably expressed the three tick inotocin receptors in Chinese Hamster Ovary cells and found that each of them was activated by nanomolar concentrations of tick inotocin (EC for ITR1 = 1.6 × 10 M; EC for ITR2 = 5.8 × 10 M; EC for ITR3 = 9.3 × 10 M), thereby establishing that they are genuine tick inotocin receptors.
PubMed: 37716155
DOI: 10.1016/j.bbrc.2023.09.009 -
Journal of Neurotrauma Feb 2020Brain edema formation contributes to secondary brain damage and unfavorable outcome after traumatic brain injury (TBI). Aquaporins (AQP), highly selective water...
Brain edema formation contributes to secondary brain damage and unfavorable outcome after traumatic brain injury (TBI). Aquaporins (AQP), highly selective water channels, are involved in the formation of post-trauma brain edema; however, their regulation is largely unknown. Because vasopressin receptors are involved in AQP-mediated water transport in the kidney and inhibition of V receptors reduces post-trauma brain edema formation, we hypothesize that cerebral AQPs may be regulated by V receptors. Cerebral and messenger ribonucleic acid (mRNA) and AQP1 and AQP4 protein levels were quantified in wild-type and V receptor knockout mice before and 15 min, 1, 3, 6, 12, or 24 h after experimental TBI by controlled cortical impact. In non-traumatized mice, we found AQP1 and AQP4 expression in cortical neurons and astrocytes, respectively. Experimental TBI had no effect on mRNA or AQP4 protein expression, but increased mRNA ( < 0.05) and AQP1 protein expression ( < 0.05) in both hemispheres. The mRNA and AQP1 protein regulation was blunted in V receptor knockout mice. The V receptors regulate cerebral AQP1 expression after experimental TBI, thereby unraveling the molecular mechanism by which these receptors may mediate brain edema formation after TBI.
Topics: Animals; Aquaporin 1; Brain Edema; Brain Injuries, Traumatic; Cerebral Cortex; Male; Mice; Mice, Knockout; Receptors, Vasopressin
PubMed: 31547764
DOI: 10.1089/neu.2019.6653 -
Anesthesiology Sep 2018WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Recovery from pain after surgery is faster after cesarean delivery than after other abdominal procedures. The...
WHAT WE ALREADY KNOW ABOUT THIS TOPIC
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Recovery from pain after surgery is faster after cesarean delivery than after other abdominal procedures. The authors hypothesized that recovery in rats after surgery could be reversed by antagonism of spinal oxytocin or vasopressin receptors, that there may be a sex difference, and that spinal oxytocin innervation could change after surgery.
METHODS
Male and female rats underwent partial spinal nerve ligation surgery. Effects of nonselective and selective oxytocin and vasopressin 1A receptor antagonists on mechanical hypersensitivity during partial recovery were assessed (n = 8 to 14/group). Oxytocin immunoreactivity in the dorsal horn of the spinal cord (n = 7 to 8/group) and messenger RNA (mRNA) expression for oxytocin-binding receptors in dorsal root ganglia and spinal cord (n = 8/group) were measured.
RESULTS
Intrathecal injection of oxytocin and vasopressin receptor antagonists were similarly effective at reducing withdrawal threshold (in all experiments from 22 [19, 26] median [first quartile, third quartile]) g to 8.3 [6.4, 12] g after injection) in both sexes, while having no or minimal effects in animals without surgery. Oxytocin fiber immunoreactivity was 3- to 5-fold greater in lumbar than other regions of the spinal cord and was increased more than 2-fold in lumbar cord ipsilateral to surgery. Injury was also associated with a 6.5-fold increase in oxytocin receptor and a 2-fold increase in vasopressin 1A receptor messenger RNA expression in the L4 dorsal root ganglion ipsilateral to surgery.
CONCLUSIONS
These findings suggest that the capacity for oxytocin signaling in the spinal cord increases after surgery and that spinal oxytocin signaling plays ongoing roles in both sexes in recovery from mechanical hypersensitivity after surgery with known nerve injury.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Female; Hyperalgesia; Injections, Spinal; Ligation; Male; Oxytocin; Pain, Postoperative; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Receptors, Vasopressin; Recovery of Function; Signal Transduction; Spinal Nerves
PubMed: 29912007
DOI: 10.1097/ALN.0000000000002290