V1b Receptors: New Probes for Therapy

The wide range of physiological effects mediated by arginine vasopressin (AVP) raises the possibility that pharmacological agents selectively targeting different components of this peptide system may provide potential novel therapeutic approaches for the treatment of human diseases. AVP receptor subtypes have been proposed as potential targets for the treatment of debilitating disorders such as congestive heart failure, arterial hypertension, dysmenorrhea (V1a receptors), hyponatremia, water retention, ocular hypertension (V2 receptors), and pre-term labor (oxytocin (OT) receptors) (1). AVP effects are mediated by three 7-transmembrane G protein-coupled receptors that have been defined on the basis of their tissue distribution and pharmacology. The V1a receptor subtype is widely distributed in the vascular wall, central nervous system, liver, kidney, and platelets; V1b receptors are predominantly found in the anterior pituitary. The V2 receptor subtype is distributed almost exclusively in the kidney. Furthermore, AVP binds with appreciable affinity and has agonist activity at the OT receptor, which also belongs to the G protein-coupled receptor superfamily (2).