L10 Flashcards
describe a general cellular signaling/signal transduction pathway in the epithelia
you start with a stimulus which causes a ligand to be released
a liggened is a hormone, growth factor or another metabolite
that ligand will then bind to its receptor either in the membrane or cytoplasm
this activates a signal transduction pathway causing a cellular response
this then acts as negative feedback to the stimulus OR can cause other intracellular mechanisms
describe how water soluble and lipid soluble get to their receptors
water are soluable in blood therefore they cant get through the membrane and have to bind to a membrane receptor
lipid soluble are carrier through the blood on a carrier protein which they will disassociate from to diffuse through the membrane
what is the effect of lipid soluble ligands
they effect gene transcription
what effects happen faster. water soluble or lipid soluble
why
water
this is because lipid have to activate gene transcription to have an effect
what has longer lasting effects water soluble or lipid soluble
why
lipid because it alters gene expression
describe the signal transduction pathway for water soluble ligands
the signaling molecule binds to the membrane receptor
this activates intracellular signaling pathways which activate target proteins causing an effect
what is a basic overview of how G coupled protein receptors work
When a ligand binds to the receptor , the G protein will interact with it causing a conformational change. This leads to GDP –> GTP
The G protein then dissociates which allows the G protein to interact with its effector molecules
what is the role of effectors in the G coupled proetin receptor pathway
promote an increase in second messengers leading to cellular response
list some second messengers
cAMP, Ca2+, IP3, diacylglycerol
what is the function of the kidney
to filter blood removing wastes and extra water to make urine
it also reabsorbs needed substances and returns them to the blood therefore having an effect on blood pressure
what is the role of the proximal convoluted tuble
it reabsorbs all glucose and amino acids and most mineral salts
it also reabsorbs most water
what is the role of the loop of henle
reabsorbs some water
what is the role of the distal convoluted tuble
some mineral salts and water
what does the collecting duct contain
metabolic waste (eg ureia, creatine and uric acid) and excess water and mineral salts
what are the 4 hormones that regulate the kidneys function
angiotensin 2, aldosterone, ANP and antidiuretic hormone
what is the role of ANP
atrial natriuretic peptide (ANP), guanylin, and dopamine: decrease NaCl and water reabsorption
what also acts like ANP
guanylin, and dopamine
what is the role of antidiuretic hormone/vasopressin
mainly increases water reabsorption
what 2 hormones have the same effect
angiotensin 2 and aldosterone
what is the role of angiotensin 2 and aldosterone
increase NaCl and water reabsorption
what hormones have the opposite effect from each other
angiotensin 2 and aldosterone have the opposite effect to ANP
why and how is angiotensin 2 synthesized
Low perfusion pressure in kidneys, decrease in NaCl to macula densa
Renin (from kidney) cleaves angiotensinogen (from liver) to form angiotensin I which is further cleaved by ACE to form angiotensin II
this is a water soluble ligand which receptor is located in the adrenal gland
where is ANGII receptor located
ANGII binds to AT1 receptor (GPCR) on zona glomerulosa cells of adrenal cortex
what happens when ANGII binds to its receptor
the receptor is a G coupled protein receptor and when ANGII is bound it activates a Gq pathway
which causes Ca to be released from the ER which drives aldosterone to be synthesised and released
describe the Gq pathway
When the first messenger binds which causes the GDP to be nocked off and replaced by GTP and then the alpha subunits separates from the beta and the gamma.
The alpha subunits then activates phospholipase C. Phospholipase C then generates a triphosphate and diacylglycerol which leaves the membrane which are the second messenger.
The IP3 activates receptors which are located on the ER which allows the ligand gated ion channels on the ER to release CA2+. That Ca2+ then goes on to stimulate processes which are Ca2+ dependent.
DAG activates protein kinase c which phosphorylates other molecules which will then mediate the cells response
Angiotensin 2 binds to its receptor in the plasma membrane
BECAUSE
angiotensin 2 is a lipid-soluble ligand
the first is true and the second is false
ANGII is water soluable. what is aldosterone
it is a steroid hormone therefore it is lipid soluable
what is the role of aldosterone
it increases Na uptake from the kidney tubules therefore increasing blood pressure
describe steroid hormone signal transduction
the steroid hormone will bind to its receptor in the cytoplasm which is the early primary response
then the complex translocates to the nucleus where it activates primary response genes
the proteins made by the primary response genes will either cause the cellular response or they will o back and activate secondary response genes which produce secondary response proteins which will cause an effect
primary response proteins also switch off primary response genes
what is the receptor for aldosterone
the mineralocorticoid receptor. this is a cytoplasmic receptor
what gene does the aldosterone receptor complex activate
the SGK gene
what does SGK do
it decreases ENaC endocytosis and degradation (primary response) (stops it from getting broken down)
AND
promotes transcription of secondary response genes such as producing more ENaC
what does the primary and secondary response of SGK cause
Both lead to increased Na+
transport, increased Na+ in ECF, water retention and thus an increase in blood
volume and blood pressure.
what is the target cell of aldosterone
the principal cells of the kidney collecting duct
what leads to the switching off of the angiotensin 2 signal transduction pathway
when normal blood pressure is sensed in the kidneys it causes negative feedback causing renin (therefore ANGII) levels to decrease
angiotensin 2 receptors are endocytosed
We get the activation of a GTPase inside the zonular gradulocer cells therefore even if the ligand binds to the receptor and causes the formation of GTP it will get cleaved immediately meaning that phospholipase C cant be activated
We also get increased expression of a Ca pump on the ER membrane meaning that if IP3 caused the release of Ca then it will just get pumped back into the ER
therefore aldosterone levels are decreased
when is ANP released
in response to high blood pressure to decrease blood volume and pressure
where is the ANP receptor located
in the basolateral membrane
what kind of receptor is the ANP receptor
it is a dimer which is enzyme linked
what enzyme is the ANP receptor linked to
guanylyl cyclase
what is the role of guanylyl cyclase
it catalyses the reaction of GTP –> cGMP
what does cGMP activate
protein kinase G which decreases Na/K pump activity
describe ANP signal transduction pathway
increases ESF/BP leads to atrial stretch causing ANP to be released from the heart
ANP then binds to its receptor on the basolateral membrane of the collecting duct epithelial cell
guanylyl cyclase activity of the receptor increases cGMP which activates protein kinase G
Na/K ATPase phosphorylation (by PKG) and activity decrease in Na transport across the epithelium decreases therefore BP decreases
what is the negative feedback loop for ANP
less stretch on the atrial walls causes the ANP receptor to be endocytosed from the membrane and phosphodiesterase to be activated
what is the role of phosphodiesterase in ANPs negative feedback loop
it catalyses cGMP –> GMP and deactivates PKG
how does ADH increase water reabsorption
through aquaporin 2 in the distal kidney
how does aquaporin 2 get inserted into the apical membrane
ADH binds to its receptor (V2) which is a GPCR. the G protein activates adenylyl cyclase which activates PKA which phosphorylates aquaporin 2
aquaporin2 is usually sitting in vesicles inside the cell but when it is phosphorylated in signals the cell to exocytose them into the apical membrane
they are now able to reabsorb water from the urine to inside of the distal kidney cell
after water has traveled into the cell via aquaporin2, how does it get into the blood
aquaporin 3 and 4 are located in the basolateral membrane
describe the signal transduction pathway for ADH
ECF osmolarity increases causing ADH to be released from the posterior pituitary
ADH binds to the V2 receptor which is GPCR on the basolateral membrane of the cortical collecting duct principal cells
adenylyl cyclase is activated increasing cAMP, activating PKA which phosphorylates A2 causing it to be exocytosed into the apical membrane
A2 transports water into the cells and A3 and 4 export it out into the ECF
describe the negative feedback loop for ADH
when ECF osmolarity goes back to normal it causes negative feedback to the posterior pituitary meaning no ADH is secreted
V2 is endocytosed and no receptor means no intracellular signalling therefore less water is reabsorbed
