Disease relevance of AVPR1B

• Isolation of the cDNAs encoding the V1a and V1b receptor subtypes explained the tissue variability of V1 antagonist binding, whereas identification of the cDNA and gene encoding the V2 receptor provided the information to identify the mutations responsible for X-linked nephrogenic diabetes insipidus [1].
• Small-cell lung cancer and breast cancer cells also express normal genes for all vasopressin receptors and produce normal vasopressin receptor mRNAs and V1a and V1b receptor proteins, and the vasopressin-activated calcium mobilising (VACM) protein; plus both normal and abnormal forms of the V2 receptor [2].

Psychiatry related information on AVPR1B

• Antagonist treatment together with other sophisticated loss-of-function and gain-of-function approaches provide evidence for a multiple involvement of V1a and V1b receptor subtypes in stress-related behavior and disorders, including anxiety disorders, comorbid depression and their neuroendocrine concomitants [3].
• As such, antagonists of the CRF1 and V1b receptor subtypes are being developed as potential treatments for affective disorders [4].
• The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats [5].

High impact information on AVPR1B

• We have previously demonstrated that a mutation of the hydrophobic motif 341FNX2LLX3L350 in the C terminus of the human pituitary vasopressin V3 receptor (MUT V3R) led to it being retained in the endoplasmic reticulum (ER) [6].
• It binds various agonists and antagonists of vasopressin with affinities distinct from those of V1a and V2 receptors but consistent with those anticipated for the V1b receptor on the basis of the pharmacological studies [7].
• Release is mediated by the V1b receptor through the mobilization of intracellular Ca2+ by phosphatidylinositol hydrolysis [7].
• The inhibitory effects of vasopressin antagonists on AVP-induced insulin release correlate well with the rank order of potency to inhibit [3H]AVP binding to the V1b receptor; pancreatic islet cells were significantly inhibited by SSR149415 but not by SR49059 or OPC-21268 [8].
• By contrast, the V1b receptor subtype was only expressed in medullary chromaffin cells [9].

Biological context of AVPR1B

• Vasopressin increases GAGA binding activity to the V1b receptor promoter through transactivation of the MAP kinase pathway [10].
• The data support the hypothesis that VP contributes to pituitary V1bR upregulation during stress through GAGA binding-mediated transcriptional activation [10].
• V1bR gene transcription, which is necessary to maintain V1bR mRNA levels, depends on a number of responsive elements in the promoter region, of which the stretch of GA repeats near the transcription start point (GAGA box) is essential [11].
• This includes the repressor effect of small open reading frames (ORF) present upstream of the main V1bR ORF, and an internal ribosome entry site (IRES), which activates V1bR translation [11].

Anatomical context of AVPR1B

• By RT-PCR, we confirmed the presence of V1b receptor mRNA in both In-R1-G9 cells and in human pancreas [12].
• In addition, DDAVP dose-dependently stimulated inositol turnover in human V1b receptor-expressing COS-1 cells [13].
• These findings will allow us to better understand the physiological role of V1b receptor in pancreatic beta cells and in the renal inner medullary collecting duct, and help us to identify as yet unknown vasopressin receptors through which DDAVP cause the accumulation of intracellular Ca2+ in other tissues [13].

Associations of AVPR1B with chemical compounds

• Both during the day and night, cortisol secretion was elevated during VPa infusion, suggesting that this V1a receptor antagonist has agonist activity on the V1b receptor in the pituitary involved in vasopressin-stimulated corticotropin release [14].
• The data provide mechanisms by which regulation of hypothalamic VP and pituitary V1bR content contribute to controlling HPA axis activity during chronic stress [15].
• These effects were similar to those obtained with the V1b receptor antagonist SSR149415 (3-10 mg/kg, p.o.), diazepam (1 mg/kg, p.o.) and buspirone (10 mg/kg, p.o.). Fluoxetine and SSR240600 were devoid of effects in this test [16].

Regulatory relationships of AVPR1B

• This study demonstrates that VP stimulates GAGA binding to the V1bR promoter through transactivation of the EGFR and MAP kinase [10].

Other interactions of AVPR1B

• This long-sought selective VP V1b receptor ligand with nanomolar affinity will allow a better understanding of V1b-mediated VP physiological effects and is a promising new tool for V1b receptor structure-function studies [17].
• Using receptor selective VP analogs we showed that both V1aR and V1bR subtypes can mediate GAGA binding activation in H32 cells [10].
• In chromatin immunoprecipitation assays, VP induced RNA polymerase II recruitment by the wild type V1bR promoter but not by a construct with the major GAGA box deletion [10].
• The primary aim of the present study is to investigate the effect of the compounds acting on stress-related peptide receptors such as a vasopressin V1b receptor antagonist and a corticotropin-releasing factor CRF1 receptor antagonist in rat pup SIV [18].

Analytical, diagnostic and therapeutic context of AVPR1B

• Here we report the molecular cloning and functional expression of a complementary DNA encoding the human V1b receptor [7].

References