Vasopressin V1b receptor (V1BR) also known as vasopressin 3 receptor (VPR3) or antidiuretic hormone receptor 1B is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''AVPR1B'' (arginine vasopressin receptor 1B)

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. V1BR acts as a

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

for

vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then trave ...

. AVPR1B belongs to the subfamily of

G-protein coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s. Its activity is mediated by G proteins which stimulate a

phosphatidylinositol Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

second messenger system. It is a major contributor to homeostasis and the control of water, glucose, and salts in the blood. Arginine vasopressin has four receptors, each of which are located in different tissues and have specific functions. AVPR1b is a g-protein coupled pituitary receptor that has only recently been characterized because of its rarity. It has been found that the 420-amino-acid sequence of the AVPR1B receptor shared the most overall similarities with the AVP1A, AVP2 and oxytocin receptors. AVPR1B maps to chromosome region 1q32 and is a member of the vasopressin/oxytocin family subfamily.

Tissue distribution

AVPR1B was initially described as a novel vasopressin receptor located in the anterior pituitary, where it stimulates

ACTH Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...

release. Subsequent studies have shown that it is also present in the brain and some peripheral tissues.

Clinical significance

Behavioral

Inactivation of the Avpr1b gene in mice (knockout) produces mice with greatly reduced aggression and a reduced ability to recognize recently investigated mice.

Defensive behaviour Deimatic behaviour or startle display means any pattern of bluffing behaviour in an animal that lacks strong defences, such as suddenly displaying conspicuous eyespots, to scare off or momentarily distract a predator, thus giving the prey anim ...

and predatory behaviours appear normal in these knockout mice, but there is evidence that social motivation or awareness is reduced. The AVPR1B antagonist, SSR149415, has been shown to have anti-aggressive actions in hamsters and anti-depressant- and anxiety (anxiolytic)-like behaviors in rats. A single nucleotide polymorphism (SNP) has been associated with susceptibility to depression in humans.

Metabolic

Various stress-induced elevations of ACTH are blunted in the Avpr1b knockout mouse.

Oncology

AVPR1B is expressed at high levels in ACTH-secreting

pituitary adenoma Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.bronchial carcinoid A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchus. ...

s responsible for the

ectopic ACTH syndrome Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small-cell lung ...

Ligands

Nelivaptan Nelivaptan (INN) (developmental codename SSR-149,415) is a selective, orally active, non-peptide vasopressin receptor antagonist selective for the V1B subtype. The drug had entered clinical trials for treatment of anxiety and depression. In J ...

(SSR149415) and D- eu⁴-Lys⁸vasopressin are a specific antagonist and agonist for the vasopressin 1b receptor, respectively.

Function

AVPR1B is found in different parts of the body and thus has several influences and regulatory actions. Arginine vasopressin influences several symptoms related to affective disorders including significant memory processes, pain sensitivity, synchronization of biological rhythms and the timing and quality of REM sleep. Studies have shown that AVPR1B deficiencies produce behavioral changes that can be reversed when the peptide is replaced. These effects are expressed through contact with specific plasma membrane receptors. AVPR1B is responsible for fueling the effects of vasopressin on ACTH release. This interaction takes place as Arginine Vasopressin works with corticotropin releasing hormone to stimulate the pituitary gland to secrete ACTH. AVPR1b is then responsible for mediating the stimulatory effect of vasopressin on ACTH release. Several G proteins are also involved in the signal transduction pathways linked with AVPR1B. These relationships depend on the level of receptor expression and concentration of vasopressin. For example, AVPR1B causes secretion of ACTH from the anterior pituitary cells in a dose-dependent relationship by activating protein kinase C via the Gq/11 protein.

Application

There have been several experiments which have studied these interactions further and revealed AVPR1B's role in psychological disorders and regulatory functions. Haplotypes of AVPR1B are associated with increased protective effects to recurrent major depression. AVPR1B has also been associated with higher cortisol responses to psychosocial stress in children with psychiatric disorders compared with carriers of glucocorticoid receptor gene. AVPR1b has also shown involvement in regulation of brain water content and cerebral edema. This was revealed as increased levels of AVPR1B mRNA on the choroid plexus were discovered as a result of increased plasma osmolality. The increase after a reduction of brain water content from salt water loading indicated AVPR1B's role in the neuroendocrine feedback loop in maintaining normal central nervous system fluid balance.

References

External links

* * * * * {{Oxytocin and vasopressin receptor modulators G protein-coupled receptors