The vasopressin Avpr1b receptor: Molecular and pharmacological studies

Abstract

The distribution, pharmacology and function of the arginine vasopressin (Avp) 1b receptor subtype (Avpr1b) has proved more challenging to investigate compared to other members of the Avp receptor family. Avp is increasingly recognised as an important modulator of the hypothalamic-pituitary-adrenal (HPA) axis, an action mediated by the Avpr1b present on anterior pituitary corticotrophs. The Avpr1b is also expressed in some peripheral tissues including pancreas and adrenal, and in the hippocampus, paraventricular nucleus, and olfactory bulb of the rodent brain where its function is unknown. The central distribution of Avpr1bs is far more restricted than that of the Avpr1a, the main Avp receptor subtype found in the brain. Whether Avpr1b expression in rodent tissues is dependent on differences in the length of microsatellite dinucleotide repeats present in the 5′ promoter region of the Avpr1b gene remains to be determined. One difficulty of functional studies on the Avpr1b, especially its involvement in the HPA axis response to stress, which prompted the generation of Avpr1b knockout (KO) mouse models, was the shortage of commercially available Avpr1b ligands, particularly antagonists. Research on mice lacking functional Avpr1bs has highlighted behavioural deficits in social memory and aggression. The Avpr1b KO also appears to be an excellent model to study the contribution of the Avpr1b in the HPA axis response to acute and perhaps some chronic (repeated) stressors where corticotrophin releasing hormone (Crh) and other genes involved in the HPA axis response to stress do not appear to compensate for the loss of the Avpr1b.

Persistent Increase in Hypothalamic Arginine Vasopressin Gene Expression During Protracted Withdrawal from Chronic Escalating-Dose Cocaine in Rodents

“…In accordance with this notion, pretreatment with the selective V1b antagonist SSR149415 attenuated HPA activity during acute cocaine withdrawal. This result also suggests that the HPA activation was partially mediated through V1b receptors, which are expressed in the corticotropic ACTH-positive cells (Hernando et al, 2001), and modulate HPA axis activity in response to a variety of stressors (Roper et al, 2011) (see more discussion below).…”

“…In this experiment, rats were assigned to one of four treatment groups: (1) Acute cocaine withdrawal: n ¼ 8; (2) Saline control: n ¼ 6; (3) SSR149415 + Acute cocaine withdrawal: n ¼ 6; and (4) SSR149415: n ¼ 6. The SSR149415 dose chosen was based on previous studies, in which 1-30 mg/kg doses were observed to efficiently block HPA activation induced by a variety of stressors (Serradeil-Le Gal et al, 2002;Zhou et al, 2008b;Roper et al, 2011).…”

Hypothalamic-pituitary-adrenal axis function during perinatal depression

“…The first involves the hypothalamic magnocellular acting through its peripheral cognate V1a receptor [49,50] , a G-protein-coupled receptor signaling via phospholipase C [51][52] , is largely responsible for regulating water homeostasis and blood pressure [49,53] . The second system consists of parvocellular neurons within the PVN; these neurons produce both AVP and CRH peptide hormones [55] .…”

“…Acting through its cognate V1b receptor expressed on pituitary corticotrophs, AVP stimulates ACTH release [53,55,57] . The V1b receptor is largely responsible for regulating HPA-axis activity and responding to acute and chronic stressors in mammals [53,55] . …”

Hypothalamic‐pituitary‐adrenal axis and depression symptom effects of an arginine vasopressin type 1B receptor antagonist in a one‐week randomized Phase 1b trial

“…V 1B antagonism in limbic brain regions may also contribute to ABT‐436 efficacy. In animal models of depression and anxiety, both HPA axis and limbic V 1B receptors contribute to effects demonstrated by V 1B antagonists (Roper, O'Carroll, Young, & Lolait, 2011). …”