Disease relevance of Avpr1b

• In contrast, plasma ACTH and CORT levels induced by hypoglycemia were significantly decreased in the Avpr1b KO mice when compared with wild-type littermates [1].
• Surprisingly, our findings indicate that there is no interaction between either the Avpr1a or Avpr1b and ethanol on motor coordination, hypothermia, mood, or voluntary ethanol consumption [2].
• We suggest that V1bR antagonists could prove useful for treating aggressive behavior seen, for example, in dementias and traumatic brain injuries [3].

Psychiatry related information on Avpr1b

• Preliminary evidence suggests that female V1B receptor knockout mice could also have social memory deficits [4].
• In this study, we characterized more thoroughly the social behavior of vasopressin 1b receptor null (V1bR-/-) mice [5].
• This difference in behavior is not explained by an anosmic condition as there were no differences between V1bR-/- and V1bR+/+ mice in their abilities to detect a cookie buried in clean bedding, or in their ability to perform in an operant conditioning task using a fully automated liquid dilution olfactometer [5].
• As such, antagonists of the CRF1 and V1b receptor subtypes are being developed as potential treatments for affective disorders [6].

High impact information on Avpr1b

• AVP-induced ACTH release from primary cultured pituitary cells in V1bR-/- mice was also blunted [7].
• Fos-mapping within chemosensory responsive regions suggests that the behavioral deficits in V1bR knockout mice are not due to defects in detection and transmission of chemosensory signals to the brain [3].
• A radioligand binding study showed that SR49059 and OPC-21268 potently inhibited [3H]AVP binding to the cloned mouse V1a receptor, with Ki values of 27 and 510 nM, respectively, whereas SSR149415 potently inhibited [3H]AVP binding to the cloned mouse V1b receptor with a Ki value of 110 nM [8].
• Moreover, PPI deficits observed in the V1bR KO mice are significantly reversed by atypical antipsychotics such as risperidone and clozapine but not by a typical neuroleptic haloperidol, like in schizophrenic patients [9].
• V1bR KO mice also showed a decrease in basal levels of extracellular dopamine (DA) in the medial prefrontal cortex, which is thought to be an important brain region for PPI [9].

Biological context of Avpr1b

• In fetal thymic organ cultures, OTR antagonist d[D-Tyr(Et)2, Thr4]OVT increased early apoptosis of CD8 cells, while V1bR antagonist (Sanofi SSR149415) inhibited T-cell differentiation, and favored CD8 T-cell commitment [10].

Associations of Avpr1b with chemical compounds

• To investigate the role of Avp in the hypothalamic-pituitary-adrenal axis response to stress, we measured plasma ACTH and corticosterone (CORT) levels in Avpr1b knockout (KO) mice and wild-type controls in response to two acute (restraint and insulin administration) and one form of chronic (daily restraint for 14 d) stress [1].
• Among these three subtypes, the vasopressin V1b receptor is specifically expressed in pituitary corticotrophs and mediates the stimulatory effect of vasopressin on ACTH release [7].
• In order to confirm the identity of the sequence, the V3/V1b receptor cDNA was cloned and stably expressed in CHO-AA8 Tet-Off cells under the control of tetracycline [11].
• 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 [12].
• In V1bR-/- mice, OT-induced ACTH release was significantly inhibited by CL-14-26 at 10(-8) m and completely inhibited at 10(-7)m. These results indicate that OT induces the ACTH response via OT and V1b receptors inV1bR+/+ mice but via only OT receptors in V1bR-/- mice [13].

Other interactions of Avpr1b

• Acute restraint (30 min) increased plasma ACTH and CORT to a similar level in both the Avpr1b mutant and wild-type mice [1].
• The vasopressin 1b receptor (Avpr1b) is one of two principal receptors mediating the behavioral effects of vasopressin (Avp) in the brain [14].
• From all OT and VP receptors, only OTR was expressed by all T-cell subsets, while V1bR was found in double positive and single positive CD8 cells [10].

Analytical, diagnostic and therapeutic context of Avpr1b

• To investigate the functional roles of V1b receptor subtypes in vivo, gene targeting was used to create a mouse model lacking the V1b receptor gene (V1bR-/-) [7].
• Finally, ISHH and RT-PCR showed expression of the Avpr1b gene in the rat and human hippocampi as well [14].
• Mouse Avpr1b transcript levels were not altered in the CA2 field by restraint stress or adrenalectomy [14].

References