The vasopressin Avprlb receptor: Molecular and pharmacological studies

Abstract

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