Assignment 3

     Vasopressin has many functions in mammals other than the regulation of water retention and homeostasis. it has been seen to influence sexual behavior. This however is mostly attributed to the abundance and distribution of V1 receptors.

     The precursor sequence to vasopressin has be found and sequenced in many different mammals and members of Eutheria. Even though there is differences in vasoressin between different species there is ahighly conserved single precursor gene for vasopressin in every specie. This lack of phenotypic variability in species indicates that the structure of the hormone is important to its function and that it is quite specific. This could be in part due to its small size, only 9 amino acids. The vaiability that does exist is found in the other regions of the pro-hormone.

     Problems concerning vasopressin can arise not only when the vasopressin core protein is mutated but when the precursor protein is mutated as well. This can be a cause for diabetes insipidus. Mutations in the vasopressin pro-hormone result in large increases in urine production. Even though the vasopressin portion of the pro-hormone may not be mutated the portion of the gene encoding the neurophisin or signal peptide. Mutations in the signal peptide can result in inproper sorting in the magnocellular neurons of the supraoptic and paraventricular nuclei of the peptide. Mutations in the neurophysin can result in improper binding to vasopressin.

     The complete loss of vasopressin rats resulted in diabetes insipidus, this could however be controlled with vasopressin being taken in throught the diet. It also demonstrated that there was a decrease in the stress response of the rats as well. Even single nucleotide polymorphisms can have drastic effects on the stress response and anxitey. At the genomic level a change from an adenine to a guanine changes how vasopressin is represed by CArG binding factor. This is leads to vasopressin over expression.

     Vasopressin primarily acts on two classes of receptor, the V1 and V2 receprots. V1 receptors have been found in smooth muscle, liver and kidneys, this could be attributed to its ability to act on water retention and homeostasis. These receptors are also found in the brain and have been linked to the regulation of social behavior. The V2 receptor is found in periferal tissues. Vasopressin works to bind to the V2 receptor by binding with the alpha subunit of the of the G-protein. There is a lot more variatioon in these receptors than in vasopressin itself. In  the V2 receptor the Pro322 residue is conserved allowing for movement in the recepor. There are 2 mutations linked to this residue that have been linked to nephrogenic diabetes insipidus.