Vasopressin receptor 1B

Tissue distribution

AVPR1B was initially described as a novel vasopressin receptor located in the anterior pituitary, where it stimulates ACTH 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 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 adenomas as well as in bronchial carcinoids responsible for the ectopic ACTH syndrome.

Ligands

Nelivaptan (SSR149415) and D-[Leu4-Lys8]-vasopressin 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

References

1. (December 2003). "Science review: Vasopressin and the cardiovascular system part 1--receptor physiology". Critical Care.
2. (March 2004). "A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression". Molecular Psychiatry.
3. "anti-Arginine Vasopressin Receptor 1B (AVPR1B) antibody (ABIN122463)". antibodies-online.
4. (1984). "Evidence that the effects of arginine-8-vasopressin (AVP) on pituitary corticotropin (ACTH) release are mediated by a novel type of receptor". Peptides.
5. (2001). "Immunohistochemical localization of the vasopressin V_1b receptor in the rat brain and pituitary gland: anatomical support for its involvement in the central effects of vasopressin". Endocrinology.
6. (2006). "The Vasopressin 1b Receptor is Prominent in the Hippocampal Area CA2 Where It Is Unaffected by Restraint Stress or Adrenalectomy". Neuroscience.
7. (July 1995). "Extrapituitary expression of the rat V1b vasopressin receptor gene". Proceedings of the National Academy of Sciences of the United States of America.
8. (2016). "Molecular Neuroendocrinology: From Genome to Physiology". Wiley-Blackwell.
9. (2002). "AVPR1B knockout reduces aggressive behavior in male mice". Mol. Psychiatry.
10. (2007). "Disruption of the Vasopressin 1b Receptor Gene Impairs the Attack Component of Aggressive Behavior in Mice". [[Genes, Brain and Behavior]].
11. (2004). "Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task". Hormones and Behavior.
12. (2005). "AVP V_1b selective antagonist SSR149415 blocks aggressive behaviors in hamsters". Pharmacology Biochemistry and Behavior.
13. (2005). "An overview of SSR149415, a selective nonpeptide vasopressin V_1b receptor antagonist for the treatment of stress-related disorders". CNS Drug Reviews.
14. (2007). "The Hypothalamic-Pituitary-Adrenal Axis Response to Stress in Mice Lacking Functional Vasopressin V1b Receptors". Endocrinology.
15. (January 2011). "The vasopressin Avpr1b receptor: molecular and pharmacological studies". Stress.
16. (1997). "Ectopic ACTH production by a bronchial carcinoid tumour responsive to desmopressin in vivo and in vitro". Clinical Endocrinology.
17. (1996). "The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome". Journal of Clinical Investigation.
18. (2002). "Characterization of (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V_1b receptor antagonist". Journal of Pharmacology and Experimental Therapeutics.
19. (2007). "Pharmacological and physiological characterization of d[Leu⁴, Lys⁸]vasopressin, the first V_1b-selective agonist for rat vasopressin/oxytocin receptors". Endocrinology.
20. (August 2010). "Associations between common arginine vasopressin 1b receptor and glucocorticoid receptor gene variants and HPA axis responses to psychosocial stress in a child psychiatric population". Psychiatry Research.
21. (2001). "Salt-loading increases vasopressin and vasopressin 1b receptor mRNA in the hypothalamus and choroid plexus". Neuropeptides.