Lecture 10 things to work on Flashcards
What receptor does angiotensin 2 bind to? Where is this located?
it bind to the AT1 receptor on the zona glomerulosa cells in the adrenal cortex
What is the effect of angiotensin 2 binding to the AT1 receptor on the zona glomerulosa cells in the adrenal cortex?
This receptors is a G-protein coupled receptor which means that when angiotensin 2 binds to it, the G-protein becomes associated with the receptor. The α subunit dissociates and this activates phospholipase C which activates second messengers DAG and IP3. IP3 opens a Ca2+ channel in the SR which increases the intracellular calcium concentration. DAG activates PKC. The overall effect of these two things is that there is synthesis and release of aldosterone from these cells.
Which cells does aldosterone affect?
They affect the principle cells of the cortical collecting duct.
What happens when aldosterone binds to its receptor? Which receptor is this and where is it located?
Aldosterone is a steroid hormone which means that it can go straight through the cell membrane into the cell. It binds to a mineralocorticoid receptor. This forms a receptor complex and this travels into the nucleus.
This complex activates the transcription of SGK genes. The purpose of this is to stop ENaC endocytosis and to synthesise more ENaC. This means that ENaC remains in the membrane which means that there is increase Na+ reabsorption (and water reabsorption).
What is the purpose of angiotensin 2/aldosterone?
This is to increase the Na+ and water absorption in the cortical collecting duct principle cells to increase blood pressure.
What is the negative feedback for angiotensin 2/aldosterone?
If there is no longer a decrease in blood pressure, the levels of renin and angiotensin 2 decrease, AT1 is endocytosed, GTPase and the Ca2+ then switch off the signalling pathway
What cells do ADH affect?
This affects the principle cells in the cortical collecting duct
What causes the release of ADH?
a decrease in the ECF osmolarity
What type of receptor is the V2 receptor?
This is a GPCR receptor
What happens when ADH binds to its V2 receptor?
The G-protein dissociates and activates adenylyl cyclase which converts ATP to cAMP. This activates PKA which phosphorylates the AQP2 receptor so it moves into the apical membrane.
What is the negative feedback loop for the regulation of ADH release?
When the ECF osmolarity returns to normal, there is no ADH being released from the posterior pituitary gland. The V2 receptor is endocytosed which means that there is no cAMP increase, no activation of PKA and no phosphorylation of AQP2 channels. This leads to less water absorption.
What is ANP released in response to?
it is released in response to high blood pressure
What type of receptor is the ANP receptor and where is this located?
it is an enzyme linked receptor on the basement membrane of collecting duct epithelial cells
What happens when ANP binds to its receptor?
The receptor contains a guanylyl cyclase enzymatic domain which converts GTP to cGMP. This activates PKG which phosphorylates Na+/K+ ATPase to decrease the activity of the pump, so the transport of Na+ across the epithelium decreases
