V_1a Vasopressin Receptors: Selective Biotinylated Probes

The multiple actions of the neurohypophyseal hormone [Arg8]vasopressin (AVP) are mediated by at least three pharmacologically distinct subtypes of AVP receptors (VPR), located in the plasmalemma of AVP-responsive cells. The V1a subtype of VPR is characterized and distributed in mammalian tissues. Functional studies have shown that the V1a VPR is functionally coupled to phosphoinositidase C and mediates the actions of AVP in vascular smooth muscle, liver, and other sites in the brain and periphery. This chapter discusses many synthetic analogs of AVP, and explains how much progress has been made in the design of receptor subtype-selective AVP analogs. Moreover, antagonists are now available that bind selectively and with high affinity to the V1a VPR subtype. These selective ligands have facilitated a complete pharmacological characterization of vasopressin receptor subtypes. In addition, selective AVP antagonists have therapeutic potential for selectively controlling specific actions of AVP in normal and pathological conditions. Biotinylated VPR antagonists that maintain high affinity and selective binding for V1a receptors would be versatile probes. Such probes would offer a means of selectively localizing the V1a receptor using avidin conjugated to electron-dense or fluorescent markers. In addition, biotinylated ligands can be used to develop a biospecific affinity column based on biotin–avidin complex formation.