Humans ; Tolvaptan/therapeutic use* ; Ascites/drug therapy* ; Receptors, Vasopressin ; Liver Cirrhosis/drug therapy* ; Sodium

OBJECTIVE: To explore the clinical characteristics, genetic basis and clinical treatment of seven neonates with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of the patients were collected. High-throughput sequencing was carried out to detect potential variants. Sanger sequencing was used to verify the results. RESULTS: The patients were all males, with the age of onset being 10 to 21 days. All patients were admitted to the hospital for intermittent fever as the first symptom during the neonatal period. Additional symptoms had included polydipsia and polyuria. After the treatment, 5 patients had recovered, the remainders still had NDI symptoms and developmental retardation. Five children were found to harbor pathogenic variants of the AVPR2/AQP2 gene, which included one in-frame mutation of c.645_646insGCACCTACCCTGGGTATCGCC, two missense mutations of c.541C>T and c.419C>A, and two hemizygous deletions of the AVPR2/AQP2 gene. Among these, two were unreported previously. Cases 6 and 7 were a pair of twins. Both had carried homozygous missense variants of c.538G>A of the AVPR2/AQP2 gene, which was known to be pathogenic. CONCLUSION AVPR2/AQP2 is the main pathogenic gene for congenital NDI, for which two novel pathogenic variants have been discovered in this study. Above results have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.
Aquaporin 2/genetics* ; Child ; Diabetes Insipidus, Nephrogenic/genetics* ; Diabetes Mellitus ; Humans ; Infant, Newborn ; Male ; Molecular Biology ; Mutation ; Pedigree ; Receptors, Vasopressin/genetics*

OBJECTIVE: To detect potential variant in a male neonate affected with congenital nephrogenic diabetes insipidus (CNDI). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the child and his parents. The whole coding regions of the arginine vasopressin V2 receptor (AVPR2) gene were amplified by PCR and subjected to Sanger sequencing. RESULTS: The patient presented recurrent fever and polyuria after birth. Multiple blood gas analyses indicated hypernatremia. Ultrasound showed bilateral hydronephrosis and hydroureter. The patient was partially responsive to hydrochlorothiazide. DNA analysis identified a hemizygous frameshift variant c.890-899delACCCGGAGGC in exon 2 of the AVPR2 gene in the proband. His mother was heterozygous for the same variant. CONCLUSION The c.890-899delACCCGGAGGC variant of the AVPR2 gene probably underlies the CNDI in the child. Above discovery has enriched to spectrum of CNDI associated variants.
Adult ; Diabetes Insipidus, Nephrogenic/genetics* ; Exons ; Female ; Frameshift Mutation ; Humans ; Hydrochlorothiazide/therapeutic use* ; Infant, Newborn ; Male ; Pedigree ; Receptors, Vasopressin/genetics*

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.
Aquaporin 2 ; Arginine Vasopressin ; Body Water ; Cell Membrane ; Diabetes Insipidus, Nephrogenic ; Gene Expression Regulation ; Homeostasis ; Kidney ; Kidney Tubules, Collecting ; Osmolar Concentration ; Permeability ; Phenobarbital ; Receptors, Vasopressin ; Water

OBJECTIVE: To explore the genetic basis for pedigree affected with hereditary nephrogenic diabetes insipidus (HNDI). METHODS: Next generation sequencing (NGS) with an osteology system gene panel was carried out for the proband. Suspected mutation was validated by Sanger sequencing of two relatives with similar symptoms and two unaffected relatives from the pedigree. RESULTS: The proband was found to carry a c.856C>T mutation of the AVPR2 gene. The same mutation was detected in the two relatives with similar symptoms and one unaffected healthy relative. CONCLUSION The HNDI in this pedigree may be attributed to the c.856C>T mutation of the AVPR2 gene.
Diabetes Insipidus, Nephrogenic ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Pedigree ; Receptors, Vasopressin

Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by d(CH₂)₅[Tyr(Me)²,Dab⁵] AVP, a vasopressin-1a (V1a) receptor antagonist, but not by desGly-NH₂-d(CH₂)₅[DTyr², Thr⁴]OVT, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.
Analgesia* ; Calcium ; Diagnosis-Related Groups ; Electrophysiology ; Fura-2 ; Ganglia, Spinal* ; Humans ; Injections, Intraperitoneal ; Neurons ; Oxytocin* ; Potassium* ; Receptors, Oxytocin ; Receptors, Vasopressin ; Rodentia ; Spinal Nerve Roots*

This study was aimed to investigate the effect and mechanism of Zhenwu Tang on AVP-V2R-AQP2 pathway in NRK-52E cells . Forty eight male SD rats were randomly divided into eight groups with 6 animals in each group. Distilled water or 22.68 g·kg⁻¹·d⁻¹ Zhenwu Tang(calculated by raw drug dosage meter) was given by gavage. Blood samples were collected by cardiac puncture， and the medicated serum was centrifuged from the blood by 3 000 r·min⁻¹. NRK-52E cells were treated with different medicated serum or dDAVP. The condition of cell proliferation was detected by RTCA. The distribution of V2R and AQP2 in cells were detected by immunofluorescence. The expression of V2R， PKA and AQP2 were detected by Western blot and AQP2 mRNA level was detected by real-time PCR. Results showed that the level of AQP2 mRNA(<0.01) and protein expression of V2R， PKA and AQP2(<0.05， <0.01， <0.05) of Z7d group which was treated with Zhenwu Tang medicated serum for 24 h were significantly higher than that of normal rat serum group. And the expression level of V2R， p-AQP2 and AQP2(<0.01， <0.05， <0.01) of Z7d+dDAVP group were significantly increased comparing to normal rat serum group. The results indicate that the applying of Zhenwu Tang medicated serum could increase the expression level of V2R， PKA and AQP2 which exist in AVP-V2R-AQP2 pathway in NRK-52E， and there is synergistic effect between Zhenwu Tang medicated serum and dDAVP. So the pathway of AVP-V2R-AQP2 may be one of the mechanism for which Zhenwu Tang regulate balance of water transportation.
Animals ; Aquaporin 2 ; metabolism ; Cell Line ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; cytology ; Male ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptors, Vasopressin ; metabolism ; Signal Transduction

Hyponatremia is commonly encountered in patients with heart failure and has a poor prognosis. Tolvaptan, a novel selective vasopressin V2 receptor blocker, has received attention as an effective drug for treating the syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. However, the safety of tolvaptan in the treatment of hyponatremia is not clear. We experienced a 78-year-old woman with a history of heart failure, atrial fibrillation, and hyponatremia who developed osmotic demyelination syndrome as an unexpected response to treatment with tolvaptan.
Aged ; Atrial Fibrillation ; Demyelinating Diseases* ; Female ; Heart Failure* ; Heart* ; Humans ; Hyponatremia ; Prognosis ; Receptors, Vasopressin

Amyotrophic lateral sclerosis (ALS) patients rarely present with either syndrome of inappropriate antidiuretic hormone secretion or generalized edema. Tolvaptan is a selective vasopressin V2 receptor antagonist that produces effective aquaresis, and its use in ALS patients has not been previously reported. A 50-year-old male ALS patient was admitted because of both generalized edema and dilutional hyponatremia. These manifestations were refractory to conventional diuretics and fluid therapy, but a very brisk diuresis was induced by tolvaptan administration. Edema and hyponatremia were also improved, and the patient was able to be discharged without tolvaptan. In this case report, we postulate how edema and dilutional hyponatremia developed in the patient, and discuss the mechanism of tolvaptan in treating hypervolemic hyponatremia. Further experience is necessary to evaluate the usefulness of tolvaptan in patients with neurological disorders.
Amyotrophic Lateral Sclerosis* ; Diuresis ; Diuretics ; Edema ; Fluid Therapy ; Humans ; Hyponatremia* ; Male ; Middle Aged ; Nervous System Diseases ; Receptors, Vasopressin

OBJECTIVETo detect potential mutation in a pedigree affected with congenital nephrogenic diabetes insipidus (NDI).

METHODSClinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and directly sequenced.

RESULTSThe patient presented polyuria and polydipsia postnatally. Computerized tomography revealed bilateral hydronephrosis and hydroureter. The patient was responsive to hydrochlorothiazide but not to desmopressin. DNA analysis identified a hemizygous missence mutation c.295 T>C in exon 2 of the AVPR2 gene in the proband. His mother and grandmother were both heterozygous for the same mutation.

CONCLUSIONThe congenital NDI in the patient was probably due to mutation of the AVPR2 gene.

Adolescent ; Base Sequence ; DNA Mutational Analysis ; Diabetes Insipidus, Nephrogenic ; congenital ; genetics ; Exons ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Vasopressin ; genetics