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PHSL 233 > L10 > Flashcards

L10 Flashcards

1
Q

describe a general cellular signaling/signal transduction pathway in the epithelia

A

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

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2
Q

describe how water soluble and lipid soluble get to their receptors

A

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

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3
Q

what is the effect of lipid soluble ligands

A

they effect gene transcription

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4
Q

what effects happen faster. water soluble or lipid soluble

why

A

water

this is because lipid have to activate gene transcription to have an effect

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5
Q

what has longer lasting effects water soluble or lipid soluble

why

A

lipid because it alters gene expression

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6
Q

describe the signal transduction pathway for water soluble ligands

A

the signaling molecule binds to the membrane receptor

this activates intracellular signaling pathways which activate target proteins causing an effect

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7
Q

what is a basic overview of how G coupled protein receptors work

A

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

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8
Q

what is the role of effectors in the G coupled proetin receptor pathway

A

promote an increase in second messengers leading to cellular response

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9
Q

list some second messengers

A

cAMP, Ca2+, IP3, diacylglycerol

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10
Q

what is the function of the kidney

A

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

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11
Q

what is the role of the proximal convoluted tuble

A

it reabsorbs all glucose and amino acids and most mineral salts

it also reabsorbs most water

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12
Q

what is the role of the loop of henle

A

reabsorbs some water

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13
Q

what is the role of the distal convoluted tuble

A

some mineral salts and water

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14
Q

what does the collecting duct contain

A

metabolic waste (eg ureia, creatine and uric acid) and excess water and mineral salts

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15
Q

what are the 4 hormones that regulate the kidneys function

A

angiotensin 2, aldosterone, ANP and antidiuretic hormone

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16
Q

what is the role of ANP

A

atrial natriuretic peptide (ANP), guanylin, and dopamine: decrease NaCl and water reabsorption

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17
Q

what also acts like ANP

A

guanylin, and dopamine

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18
Q

what is the role of antidiuretic hormone/vasopressin

A

mainly increases water reabsorption

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19
Q

what 2 hormones have the same effect

A

angiotensin 2 and aldosterone

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20
Q

what is the role of angiotensin 2 and aldosterone

A

increase NaCl and water reabsorption

21
Q

what hormones have the opposite effect from each other

A

angiotensin 2 and aldosterone have the opposite effect to ANP

22
Q

why and how is angiotensin 2 synthesized

A

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

23
Q

where is ANGII receptor located

A

ANGII binds to AT1 receptor (GPCR) on zona glomerulosa cells of adrenal cortex

24
Q

what happens when ANGII binds to its receptor

A

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

25
Q

describe the Gq pathway

A

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

26
Q

Angiotensin 2 binds to its receptor in the plasma membrane

BECAUSE

angiotensin 2 is a lipid-soluble ligand

A

the first is true and the second is false

27
Q

ANGII is water soluable. what is aldosterone

A

it is a steroid hormone therefore it is lipid soluable

28
Q

what is the role of aldosterone

A

it increases Na uptake from the kidney tubules therefore increasing blood pressure

29
Q

describe steroid hormone signal transduction

A

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

30
Q

what is the receptor for aldosterone

A

the mineralocorticoid receptor. this is a cytoplasmic receptor

31
Q

what gene does the aldosterone receptor complex activate

A

the SGK gene

32
Q

what does SGK do

A

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

33
Q

what does the primary and secondary response of SGK cause

A

Both lead to increased Na+
transport, increased Na+ in ECF, water retention and thus an increase in blood
volume and blood pressure.

34
Q

what is the target cell of aldosterone

A

the principal cells of the kidney collecting duct

35
Q

what leads to the switching off of the angiotensin 2 signal transduction pathway

A

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

36
Q

when is ANP released

A

in response to high blood pressure to decrease blood volume and pressure

37
Q

where is the ANP receptor located

A

in the basolateral membrane

38
Q

what kind of receptor is the ANP receptor

A

it is a dimer which is enzyme linked

39
Q

what enzyme is the ANP receptor linked to

A

guanylyl cyclase

40
Q

what is the role of guanylyl cyclase

A

it catalyses the reaction of GTP –> cGMP

41
Q

what does cGMP activate

A

protein kinase G which decreases Na/K pump activity

42
Q

describe ANP signal transduction pathway

A

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

43
Q

what is the negative feedback loop for ANP

A

less stretch on the atrial walls causes the ANP receptor to be endocytosed from the membrane and phosphodiesterase to be activated

44
Q

what is the role of phosphodiesterase in ANPs negative feedback loop

A

it catalyses cGMP –> GMP and deactivates PKG

45
Q

how does ADH increase water reabsorption

A

through aquaporin 2 in the distal kidney

46
Q

how does aquaporin 2 get inserted into the apical membrane

A

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

47
Q

after water has traveled into the cell via aquaporin2, how does it get into the blood

A

aquaporin 3 and 4 are located in the basolateral membrane

48
Q

describe the signal transduction pathway for ADH

A

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

49
Q

describe the negative feedback loop for ADH

A

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

PHSL 233 (31 decks)

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