Secondary Messenger System: Phospholipase C Mechanism

Secondary messenger systems are used by chemical messenges that are unable to cross plasma membranes and interact with the inside of cells. The types of chemical messages that utilize these systems are the polar messengers (peptides, proteins, amines {except thyroid hormone}). Secondary messenger systems have these few basic components:

• G proteins - G = guanosine triposphate (GTP) binding proteins. G proteins are attached to a portion of receptors. When activated subunits of G proteins are detached and either activate or deactivate mechanisms within the cell
• α β γ subunits - these are the units that the G proteins are made of. The alpha and beta subunits are the structural parts of the G protein while the alpha subunit is the active portion. When a G protein is activated the alpha subunit detaches it travels within the cell and can either activate or inhibit certain actions.

This mechanism consists of receptors and G proteins like the adenylyl cyclase system but that is the only realy similarity. Instead of adenylyl cyclase another enzyme called phospholipase C is activated by the dissasociated α subunit of the G protein. This also activates other secondary messenger systems within the cell as well in the following steps:

1. a hormone or neurotransmitter binds to a surface receptor which creates a conformational (shape) change with the receptor itself
2. the conformational changes causes the α subunit of the G protein to detach (disassociate)
3. the α subunit of the G protein interacts with the membrane bound enzyme called phospholipase C; this activates the enzyme
4. once activated phospholipase C catylizes (breaks down) phospholipids within the cell membrane into two specific molecules: DAG and iP3
5. Dag acts just like cAMP in the adenylyl cyclase mechanism and activates protein kinases, which in turn activates enzymatic pathways
6. iP3 interacts concurrently interacts the smooth ER of the cell and stimulates the release of calcium (Ca²), the calcium then binds with proteins and activates enzymatic pathways
7. DAG and iP3 are the secondary messengers in this system since the elicited the responses within the cell

*Chemical messengers that utilize this particular system are: GnRH, TRH, GHRH, Angiotensin II, ADH, oxytocin, α¹ receptors

*Costanzo, Linda. Board Review Series: Physiology, 2nd Edition. Baltimore, Lippincott Williams & Wilkins, 1998. Print

Here is a useful link that will take you through this step by step:

http://www.physiol.med.uu.nl/interactivephysiology/ipweb/systems/buildframes.html?endocrine/acthorm/01