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Vasopressin receptor 1A, Vasopressin receptor 1B, Vasopressin receptor 2 (V1A (AVPR1A), V1B (AVPR1B), V2 (AVPR2))

Target
V1A (AVPR1A), V1B (AVPR1B), V2 (AVPR2)
Molecular classification
G protein-coupled receptor, Receptor
01

Overview

Vasopressin receptors 1A, 1B, and 2 are **G protein-coupled receptors** for arginine vasopressin, mediating its diverse physiological actions. Vasopressin receptor 1A (AVPR1A) is primarily expressed in vascular smooth muscle, liver, brain, and other tissues, mediating vasoconstriction and modulating social and stress-related behaviors. Vasopressin receptor 1B (AVPR1B) is mainly located in the anterior pituitary and some brain regions, where it regulates the stress response by stimulating ACTH release as part of the HPA axis. Vasopressin receptor 2 (AVPR2) is highly expressed in the renal collecting ducts and mediates antidiuretic effects by promoting water reabsorption, as well as in some extrarenal tissues. Dysfunction in these receptors is associated with a range of diseases including diabetes insipidus, SIADH, cardiovascular diseases, and some behavioral and neuropsychiatric disorders. Various antagonists and agonists for these receptors are in clinical use or development.

Other names
V1a receptorAVPR1AArginine vasopressin receptor 1AAntidiuretic hormone receptor 1AV1-vascular vasopressin receptorV1b receptorAVPR1BArginine vasopressin receptor 1BPituitary vasopressin receptorV3 receptorV2 receptorAVPR2Arginine vasopressin receptor 2Renal vasopressin receptor
02

Mechanism of action

Vasopressin receptor antagonists block binding of vasopressin/ADH, thereby inhibiting downstream G protein pathways—leading to aquaresis (water excretion without sodium loss) or suppression of ACTH or vasoconstriction, depending on the receptor expressed. Agonists mimic vasopressin action, enhancing water reabsorption (V2), increasing vasoconstriction (V1A), or stimulating ACTH release (V1B).

03

Biological functions

Signal transductionVasoconstrictionCentral nervous system functions (e.g. social behavior, stress response)Regulation of blood pressureRegulation of the hypothalamic-pituitary-adrenal (HPA) axisStimulates ACTH (adrenocorticotropic hormone) releaseStress response and behaviorRenal water reabsorptionMaintenance of water homeostasis
04

Disease associations

Cardiovascular disease (hypertension, heart failure)Neuropsychiatric and behavioral disorders (autism spectrum disorder, addiction)Disorders of the HPA axis (Cushing’s disease, mood disorders, stress-related disorders)Pituitary tumorsNephrogenic diabetes insipidus (NDI), caused by receptor mutationsSyndrome of inappropriate antidiuretic hormone secretion (SIADH)Heart failure and hyponatremia
05

Safety considerations

Hyponatremia and osmotic demyelination syndrome with V2 antagonistsBlood pressure changes (hypotension/hypertension risks) with V1A antagonists or agonistsOff-target endocrine effects, e.g. ACTH suppression with V1B antagonists
06

Interacting drugs

Conivaptan (V1A/V2 antagonist)

6 more in the full profile.

07

Biomarkers

Genetic variants (VNTRs in AVPR1A, known mutations in AVPR2)AVPR2 mutations for diabetes insipidusPlasma vasopressin or copeptin as surrogate (indirect)

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