nd messengers and increase in intracellular calcium resulting in vasoconstriction. The receptor is expressed in vascular smooth muscle and also in the liver, platelets and the brain. The susceptibility of the receptor to cellular proteases has made its study rather difficult. The human type 1b (AVPR1B), also known as vasopressin receptor 3 receptor is expressed in the pituitary and due to its scarcity is the least characterized system (not shown). Vasopressin signaling via receptor type 1 is also believed to mediate behavioral effects. An important and probably the best characterized role of Avp is in the regulation of water homeostasis by signaling via receptor type 2. Water homeostasis is maintained through the regulation of intravascular blood volume and osmolality; the regulation of water excretion by the kidney represents an essential aspect. Most of the water filtered by the glomeruli is constitutively reabsorbed; a percentage of it is reabsorbed in the renal collecting duct. Avp signaling via receptor type 2 (Avpr2) mediates the process by regulating the translocation of aquaporin channel 2 (Aqp2) from intracellular vesicles to the apical plasma membrane. Avpr2 couples to Gs alpha subunit leading to activation of adenylyl cyclase (ACs), subsequent production of cyclic AMP and triggering of protein kinase A pathway. PKA signaling, a widely used intracellular pathway, is the major route for channeling the cAMP signal. PKA regulates both the translocation and the expression of Aqp2. PKA phosphorylation at serine 256 of human AQP2 is essential for translocation of the channel; PKA phosphorylation of transcription factor Creb at serine 133 leads to its activation and subsequent transcription of Aqp2, one of Creb’s many targets. PKA also regulates its own activity by phosphorylating and activating the phosphodiesterases that hydrolyze and terminate the cAMP signal. Calcium appears to mediate a cAMP dependent but PKA independent mechanism of Aqp2 translocation. As cAMP activates Creb, transcription of Aqp2 could be promoted by routes that do not involve PKA signaling. Alterations in vasopressin signaling pathway have been associated with septic shock and nephrogenic diabetes insipidus. The diagram presents an overall picture of vasopressin roles and signaling via receptor type 1 and receptor type 2 and associated intracellular pathways. For more details, check the diagrams for vasopressin signaling pathway via receptor type 2 and the protein kinase A (PKA) signaling pathway – a main route mediating Aqp2 translocation and expression. To see the ontology report for annotations, GViewer and download click here...(less)