Question

4.4 Explain how amplification occurs in signal transductions via illustrating (drawing) and discussing the actions of Vasopressin, which is a small peptide hormone, which has a specific membrane GCPR that uses inositol-1,4,5-trisphosphate (IP3) to trigger phosphorylation of Protein Kinase C. Ensure you name the all the components (10 Marks).

Answer 1

Many cellular signalling pathways are amplifying in nature which means one ligand can activate many downstream target molecules.

Vasopressin, also called Antidiuretic Hormone (ADH), is hormone containing nine amino acids synthesized in the hypothalamus.

It is important for many terrestrial animals and human to conserve water in hypernatremia or hypovolaemia condition. Vasopressin is released by pituitary gland and bind to its receptor in renal principal cells. Vasopressin controls the rate of water excretion into the urine, thus helping to control the concentration of water in the body fluids.

There are three subtypes of Vasopressin receptors - V1a, V1b and V2 receptors. V1a and V1b receptors activate phospholipases via Gq/11, and the V2 receptor activates adenylyl cyclase by interacting with Gs.

1. Binding of Vasopressin to V2R lead to dissociation heterotrimeric Gs –GTP into its α and βγ subunits. The α subunit activates adenylyl cyclase to produce cAMP from ATP. Increase in cytoplasmic cAMP activates PKA (protein kinase A) which inserts the preformed water channel aquaporin (AQP-2) into the luminal surface of the tubular cell. The βγ subunits dimer dissociated may stimulate the PLCb (phospholipase Cb) activity.

2. Ligand binding to V1 receptors dissociates Gq/11–GTP. The αq-subunit stimulates the PLCb activity which promotes hydrolysis of PIP2 (phosphatidylinositol (4,5)-bisphosphate), into DAG (diacylglycerol) and IP3 (inositol (1,4,5)-trisphosphate). IP3 in turn binds and stimulates the IP3R in the membrane of the endoplasmic reticulum and promotes Calcium release from intracellular stores.

So, here in this case, Vasopressin receptor is a G-protein coupled receptor (GPCR). Activation of one receptor lead to activation of many downstream molecules. Vasopressin bind and activates GPCR which dissociate G protein into α and βγ subunits. Ligand bound GPCR dissociates such many G-proteins and thus activates many adenylyl cyclase. Thus amplifying the signal from single activated receptor.

Without signal amplification, the net effect of signaling pathway and target molecules is negligible.