Year 1 Endocrinology Notes – Omair Shariq 2007
Session 2 – Hypothalamus and Pituitary andPituiocrinology
2.4 Name the receptors for vasopressin and the major intracellular pathway activated through each receptor.
Two main receptors identified and sequenced- called v1 and v2 receptors. The v2 receptors are found on the baso-lateral surface on epithelial principal cells on renal collecting ducts and mediate in principal physiological action of the hormone (antidiuretic) The v1 receptors are found in other target cells. Additional receptor similar to v1 identified- called v1b, located on the adenohypophysis. All receptors have seven transmembrane domains and are coupled to G proteins.
V1 Receptors – IP3 and DAG pathways
When the ligand binds to the v1 receptor, a membrane-bound enzyme phospholipase C (PLC) is activated by the associated G protein. PLC hydrolyzes PIP2, a phosphatidylinositol, into two second messengers, inositol triphosphate (IP 3) and diacylglycerol (DAG), which then go on to increase intracellular calcium levels. Calcium ions have an affect on various metabolic pathways. DAG activates protein kinase C, which phosphorylates intracellular proteins and can act on metabolic pathways.
V2 Receptors – cAMP pathway
Receptors linked via G proteins to adenyl cyclase, which is activated when vasopressin binds. Adenyl cyclase synthesizes the second messenger cyclic adenosine monophosphate (cAMP) from ATP. cAMP then binds to and activates protein kinase A Protein kinase A activates other intracellular mediators Which increase the production and action of aquaporin-2 molecules. Vasopressin stimulates the insertion into the luminal membrane, by exocytosis, of a particular group of aquaporin water channels made by the collecting-duct cells.
2.5 Name target cells for each of the vasopressin receptors.
V1a: V1b V2
Arterial/smooth muscle (vasoconstriction, platelet adhesion) Hepatocytes (glycogenolysis) CNS neurons (behavioural and other effects, memory?) Adenohypophysial corticotrophs (enhanced ACTH release) Basolateral membrane of collecting duct (distal nephron) (water reabsorption)
2.6 List the principal physiological actions of the neurohypophysial hormones. Oxytocin
Stimulates contraction of the smooth muscle of the myometrium during parturition. Stimulates contraction of myoepithelial cells surrounding the ducts of lactating mammary glands during lactation
Vasopressin
Principal action in renal collecting duct, where it stimulates water reabsorption. Arteriolar vasoconstriction ACTH release (along with CRH) – it is an ACTH secretagogue Affect learning and memory- act as neurotransmitters/modulators
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