Lecture 10 - Signal transduction in Epithelia 1 (Renal) Flashcards
What are the steps of GPCR activation?
1) Ligand binds to receptor causing activation
2) Conformational change of G protein and exchange of GDP to GTP
3) G protein dissociates
4) Subunits and GTP interact with effectors
Effectors promote an increase in second messengers such as cAMP, Ca2+, IP3, diacylglycerol, leading to cellular response.
What occurs in the PT?
ALL glucose and amino acid reabsorption (by diffusion and active transport
Most mineral salts absorption (by osmosis)
What reabsorption occurs in DCT?
Some mineral salts (by active transport)
What hormones decrease NaCl and water reabsorption?
atrial natriuretic peptide (ANP), guanylin, and dopamine
What hormones increase NaCl and water reabsorption?
angiotensin II and aldosterone: increase NaCl and water reabsorption
What hormone increases water reabsorption?
ADH/vasopressin
What stimulates aldosterone release?
Angiotensin II signal transduction in adrenal cortex
What is released in response to low BP?
Angiotensin II - Water-soluble ligand, uses GPCR
What does ANGII act on?
ANGII binds to AT1 receptor (GPCR) on zona glomerulosa cells of adrenal cortex
What does aldosterone act on?
Aldosterone lipid-soluble ligand, uses intracellular receptor to increase Na+ uptake from kidney tubules and increase blood pressure
What is the ATI receptor?
ATI receptor is a GPCR that transduces a signal through Gaq and the second messengers DAG, IP3 and Ca2+
What does IP3 signal?
The release of Ca+ from ER
What does DAG activate?
PKC
Angiotensin 2 binds to its receptor in the plasma membrane BECAUSE angiotensin 2 is a lipid-soluble ligand
C – First statement true, second false
Water-soluble ligand
What is SGK?
Primary response gene for aldosterone
Decreases ENaC endocytosis and degradation, and promotes transcription of secondary response genes
e.g. epithelial sodium channel (ENaC).
Where does aldosterone increase Na+ transport?
CCD
What is ANP?
Atrial naturetic peptide
What is ANP released in response to?
ANP released in response to HIGH blood pressure, and decreases blood volume and pressure.
What type of receptor is the ANP receptor?
Guanylyl cyclase enzyme-linked receptor
What happens when ANP is bound to its receptor?
Conversion of GTP to cGMP
cGMP activates PKG
PKG phosphorylated Na/K-ATPase
What happens when Na/K-ATPase is phosphorylated?
Phosphorylation of Na/K-ATPase will inhibit. This stops osmotic gradient, decreasing water reabsorption and blood pressure and volume.
What activates PKG?
cGMP
Where is the ANP receptor found?
On basolateral membrane of collecting duct epithelial cell
What does phosphodiesterase catalyse?
Phosphodiesterase catalyses cGMP to GMP
What does ADH do?
ADH/vasopressin increases water reabsorption through aquaporin 2 in distal kidney
What is ADH released in response to?
Increase in ECF osmolarity - dehydration
Where is ADH released from?
Posterior pituitary
What does ADH bind to?
ADH binds V2 (GPCR) receptor on basolateral membrane of cortical collecting duct principal cell
What happens when V2 is activated?
GPCR activated, cAMP increases, PKA activated, AQP2 phosphorylated and exocytosed to apical cell surface
