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Pharmacology > SF3 Guanylate Cyclase > Flashcards

SF3 Guanylate Cyclase Flashcards

1
Q

What receptors are linked to guanylate cyclase?

A

Atrial natriuretic peptide receptor
Guanylin receptor family
Photoreceptor dark cycle

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2
Q

What is the purpose of guanylate cyclase on receptors?

A

It is to phosphorylate the GTP into cyclic GMP so that it can act as a 2nd messenger

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3
Q

Where is the atrial natriuretic peptide receptor found?

A

Within the cell membrane of cardiac cells

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4
Q

Where is the guanylate cyclase found?

A

It can be found within the ANP receptor but also cytosolically.
Both will activate cyclic GMP

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5
Q

What is the importance of guanylate cyclase domains also being found in the cytosol?

A

It means that small lipophilic molecules like nitric oxide can cross the membrane into the cell and activate the conversion to cyclic GMP

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6
Q

How does the activation of guanylate cyclase impact the cardiac system?

A

The cyclic GMP will go onto to phosphorylate protein kinase G which will result in muscle relaxation and vasodilation

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7
Q

Which other structures belong to the family of natriuretic peptides?

A

ANP - mainly in the atria
BNP - found in the brain but thought to be mostly produced by the ventricles of the heart
CNP - both in the central nervous system and the endothelium
DNP - only in reptiles

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8
Q

What is responsible for degrading natriuretic peptides?

A

Neutral endopeptidase (NEP)
Nephrilysin

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9
Q

How many types of natriuretic peptide receptors are there?

A

3
NPR A
NPR B
NPR C

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10
Q

What is different about NPR C?

A

It is dimerised even in the absence of an agonist
It is referred to as a clearance receptor
There is no catalytic activity or guanylate cyclase domain associated with it

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11
Q

Which atrial natriuretic peptides can bind to NPR A?

A

ANP
BNP

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12
Q

Which atrial natriuretic peptides can bind to NPR C?

A

All three
ANP
BNP
CNP

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13
Q

Which natriuretic peptides can bind to the NPR B?

A

CNP

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14
Q

What does natriuretic peptide receptor A do?

A

Regulates blood volume and pressure
Associated with cardiac remodelling

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15
Q

What does natriuretic peptide receptor B do?

A

Promotes growth of long bones

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16
Q

What does natriuretic peptide receptor C do?

A

It’s a clearance receptor and lack guanylate cyclase
Involved in trafficking peptides and internalising them so that they may be recycled (lysosomes)

17
Q

Is NPR C the only one that internalise the various peptides?

A

NPR A and NPR B may be able to internalise peptides but this is thought to be associated with desensitisation or signal transduction

18
Q

How many types of natriuretic peptide receptors are there thought to be be?

A

In humans there are five confirmed NPRs
The two associated with dark photoreceptor cycles are thought to be cytosolic as there’s no extracellular ligand know for them

19
Q

Describe the guanylin receptor family

A

A novel endocrine axis linking the digestive system and kidney in the regulation of salt homeostasis

20
Q

What ligands are associated with the guanylin receptor family?

A

Guanylin
Uroguanylin
Lymphoguanylin
Bacterial enterotoxins mimic the other ligands to use these receptors

21
Q

What is the physiological role of Guanylin receptors?

A

Receptors found in the intestinal mucosa will increase trans epithelial secretion of Cl-, HCO3-, H2O into the lumen
Receptors in the kidney help monitor sodium and potassium loss

22
Q

Give an example of how Guanylin receptors can be targeted by pharmaceuticals

A

Laxatives and anti diarrhoeal agents
Diuretics

23
Q

Where does the nitric oxide bind to on cytosolic guanylate cyclase?

A

The haem (Fe) group

24
Q

What conditions can be treated by prolonging the interaction of nitric oxide with the guanylate cyclase?

A

Pulmonary arterial hypertension
Acute heart failure

25
Q

Give an example of a drug that delays the dissociation of nitric oxide from the haem group

A

Riociguat
Nitric oxide sensitising drug

26
Q

What is the structure of the cytosolic guanylate cyclase?

A

2 isoforms of each subunit
Homo and hetero dimers
Haem binding domain
Dimerisation domain
Catalytic domain

27
Q

Since there are two Isoforms of cytosolic guanylate cyclase what does this mean?

A

There can be homo and heterodimers

28
Q

Is nitric oxide the only activator of cytosolic guanylate cyclase?

A

No there are nitric oxide independant activators such as cinaciguat

29
Q

How is cyclic GMP cleared from inside the cell before returning to resting levels?

A

Primarily by bind to the catalytic site of phosphodiesterases and being broken down to 5-GMP which cannot activate any of the internal structures
May also be removed from the cell all together

Pharmacology (18 decks)

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