The syndrome of inappropriate AVP (ADH) secretion (SIADH) is a common clinical problem. It is characterized by elevated plasma AVP levels, which are not appropriate based on body fluid osmolality and blood volume and pressure. This condition is also known as the syndrome of inappropriate antidiuresis (SIAD). In SIADH, the collecting duct in the kidney overexpresses water channels, leading to increased water retention. As a result, individuals with SIADH retain water, causing their body fluids to become progressively hypoosmotic. Surprisingly, their urine is more hyperosmotic than expected based on the low body-fluid osmolality. SIADH can be caused by various factors such as infections, brain neoplasms, drugs (e.g., antitumor drugs), pulmonary diseases, and lung carcinoma. These conditions can stimulate AVP secretion by affecting the neural input to the AVP secretory cells. However, small cell carcinoma of the lung itself produces and secretes several peptides, including AVP. Recently, AVP receptor antagonists like conivaptan (Vaprisol) and tolvaptan (Samsca and Jinarc) have been developed to treat SIADH and other conditions where AVP-dependent water retention occurs, such as congestive heart failure and hepatic cirrhosis.

AVP plays a crucial role in regulating water permeability in the latter part of the distal tubule and collecting duct. It also enhances the permeability of the medullary section of the collecting duct to urea. Furthermore, AVP stimulates the reabsorption of NaCl by Henle's loop's thick ascending limb, distal tubule, and collecting duct.

In the absence of AVP, the apical membrane of principal cells in the latter part of the distal tubule and along the collecting duct is impermeable to water. This is because these cells lack aquaporins, which are water channels. Consequently, without AVP, there is minimal water reabsorption in these segments of the nephron. When AVP binds to the V2 receptor located in the basolateral membrane of principal cells, it triggers the insertion of aquaporin (AQP2) water channels into the apical membrane. This allows water to enter the cell from the tubule lumen. Subsequently, water exits the cell through the basolateral membrane, which is always permeable to water due to the presence of AQP3 and AQP4 water channels. Therefore, in the presence of AVP, water is reabsorbed from the tubule lumen.

The gene responsible for the V2 receptor is located on the X chromosome. It encodes a protein consisting of 371 amino acids. This protein belongs to the receptor family with seven membrane spanning domains and is coupled to heterotrimeric G proteins.
The syndrome of inappropriate AVP (ADH) secretion (SIADH) is a common clinical problem characterized by plasma AVP levels that are elevated above what would be expected on the basis of body fluid osmolality and blood volume and pressure—hence the term inappropriate AVP (ADH) secretion (this is alternatively named syndrome of inappropriate antidiuresis [SIAD]). In addition the collecting duct overexpresses water channels (see below), thus augmenting the effect of AVP to stimulate water retention by the kidney. Individuals with SIADH retain water, and their body fluids become progressively hypoosmotic. In addition, their urine is more hyperosmotic than expected based on the low body-fluid osmolality. SIADH can be caused by infections and neoplasms of the brain, drugs (e.g., antitumor drugs), pulmonary diseases, and carcinoma of the lung. Many of these conditions stimulate AVP secretion by altering neural input to the AVP secretory cells. By contrast, small cell carcinoma of the lung produces and secretes a number of peptides including AVP. Recently, AVP receptor antagonists (e.g., the nonpeptide antagonists conivaptan [Vaprisol] and tolvaptan [Samsca and Jinarc]) have been developed that can be used to treat SIADH and other conditions in which AVP-dependent water retention by the kidneys occurs (e.g., congestive heart failure and hepatic cirrhosis).
the water permeability of the latter portion of the distal tubule and collecting duct. In addition, and importantly, AVP increases the permeability of the medullary portion of the collecting duct to urea. Finally, AVP stimulates NaCl reabsorption by the thick ascending limb of Henle’s loop, distal tubule, and collecting duct.
In the absence of AVP, the apical membrane of principal cells (see ), located in the latter portion of the distal tubule and along the collecting duct, is relatively impermeable to water. This reflects the fact that in the absence of AVP the apical membrane of these cells contains few water channels (aquaporins). Thus in the absence of AVP, little water is reabsorbed by these nephron segments. Binding of AVP to the V2 receptor located in the basolateral membrane of principal cells results in the insertion of aquaporin (AQP2) water channels into the apical membrane, allowing water to enter the cell from the tubule lumen. This water then exits the cell across the basolateral membrane, which is always freely permeable to water owing to the presence of AQP3 and AQP4 water channels. Thus in the presence of AVP, water is reabsorbed from the tubule lumen.
The gene for the V2 receptor is located on the X chromosome. It codes for a 371–amino acid protein that is in the family of receptors that have seven membrane spanning domains and are coupled to heterotrimeric G proteins. As shown in