Assignment 1

     Hormones are biological molecules that are synthesized by an organism, they are secreted in the body to regulate metabolism and other processes in the body. One of these hormones is vasopressin(VP) also known as anti-diuretic hormone(ADH). This is a peptide hormone that is stored in the anterior pituitary where it is secreted in to the blood stream. The hormone was first identified in 1895 by Oliver and Schafer they demonstrated its existence when they removed the pituitary and saw a change in blood pressure. There is more than the hormone vasopressin that is associated with the pituitary gland. It wasn't until 1952 that vasopressin was first isolated from the pituitary by Vigneau and colleagues. He was also able to isolate oxytosin and was rewarded a nobel prize in 1955 for his work on these two hormones. Much work has been done on these hormones since 1952 and a vast amount of knowledge on it functions and structure has been learned.

     Vasopressin in humans is encoded from a region on the 20th chromosome. While there are equivalent proteins in other organisms, they are found on different chromosomes, the 2nd chromosome in mice and the 3rd chromosome in rats, it is believed that vasopressin originated from the duplication of a vasotensin gene. This mutation must have taken place many millenia ago as vasopressin like molecules have been observed in invertebrates such as hydra. In bony fish the vasopressin like molecule is called vasotecin.

     In humans the gene encoding for vasopressin is located on the 20th chromosome, more specifically at the AAA61291 locust. The gene encoding for the vasopressin is 164 amino acids long. There is much modification that vasopressin undergoes before it is the 9 amino acid protein that is secreted in to the blood stream. Some of the domains that are attached before the final product is obtained is a signaling peptide (aa 1-19). There is a vasopressin/ neurophysin at the 32-122 aa region and a glycopeptide at region 124-164 of the peptide sequence. The end product for vasopressin is  Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly. The cystine residues form a disulfide bond that give a ring structure. The structure of vasopressin is very similar to the structure of oxytosin. They differ only at the 3rd and 8th position.

There are multiple levels of control that function to regulate the secretion of vasopressin. There are two receptors in the body for this purpose, one is located in the heart while the other is in the hypothalamus. The sensor in the hypothalamus measures osmatic pressure. The second sensor in the heart measures changes in blood volume. These two systems work together, as water is lost from the body blood volume goes down and the osmatic pressure in the blood stream goes up. This triggers a release of vasopressin to restore the water balance in the body and maintain homeostasis.

     One of the functions of vasopressin to maintain proper water balance in the body. This is achieved by impacting the permeability of the nephrons in the kidneys to be more permeable to water and urea. The permeability of the terminal inner mendullary collecting duct is the region of the nephron that has its permeability affected. To affect the permeability of the nephron to water vasopressin is secreted from the anterior pituitary through cyclase coupled vasoreceptor. Vasopressin then binds to V2 receptors. This results in an increase in the production of cAMP. This causes PKA to phosporylate aquaporines at select serine residues. This causes the vesicles harboring the aquaporines to insert them in to the membrane of the nephron increasing its permeability to water. This aids in water re-uptake making the urine more concentrated. The method that vasopressin works to increase the nephrons permeability is less well understood than the system for the re-uptake of water. As with water vasopressin binds to the V2 receptor which results in the increased production of cAMP. Which activates PKA and results in the phosphorylation of UT-A1 at select serine residues. Epac is then phosphorylated which results in the accumulation of UT-A1 in the apical membrane.