Tissues- Signalling between cells II Flashcards

1
Q

What are hormones referred to and why

A

Chemical messages involving hormones are often referred to as ligands as they exert their effects by binding to receptors.

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2
Q

What are receptors

A

Receptors are usually proteins that bind to chemical mediators known as ligands and upon activation they elicit an effect within a cell. The intracellular effect evoked by an occupied receptor usually arises due to any chemical messenger that is a separate entity from the receptor or ligand- second messenger

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3
Q

Describe ionotropic receptors

A

Ionotropic receptor

Ligand binding  opens ion permeable pore traversing the membrane

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4
Q

Describe G-protein coupled receptors

A

membrane
G-protein coupled receptor
Ligand binding  activates intracellular G-protein

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5
Q

Describe enzyme-linked receptors

A

Ligand binding  receptor clustering  activates internal enzymes

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6
Q

Describe intracellular receptors

A

A membrane permeable ligand binds to receptor inside cell

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7
Q

Describe the signal transduction events that take place in ionotropic receptors

A

Ligand binds to the transmembrane receptor protein via the ligand binding domain on the external surface of the receptor.
Change in conformation of channel protein  opening of a pore (incorporated within its quaternary structure)
Pore allows ions to move in or out of cell according to their respective concentration gradients

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8
Q

theList some examples of ionotropic receptors

A

Receptor: Nicotinic Acetylcholine
Ligand: Acetylcholine (ACh)
Location: Skeletal muscle, Brain
Physiological effect: Muscle contraction, Cognitive enhancement

Receptor; GABAa
Ligand: -amino butyric acid (GABA)
Location: Neuronal
Physiological effect:  neuronal excitability (inhibition)

Receptor: NMDA
Ligand: Glutamate
Effect: Synaptic plasticity and memory formation

5-HI3
5-HT
Anxiety

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9
Q

What can disfunctions in the nicotinic acetylcholine receptor lead to

A

Muscle and brain problems

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10
Q

Describe the resting state of the G-Protein complex

A

In the resting state the G protein consists of a Ga subunit, an Gby subunit, and an associated GDP molecule (not part of heterotrimer), which are in close proximity to the 7-Transmembrane receptor

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11
Q

Describe the 7-TM receptor

A

Crosses the plasma membrane 7 times, linked to the intracellular G-protein complex.

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12
Q

Describe the signal transduction events of G-protein receptors

A

7-TM receptor & heterotrimeric G-protein are inactive
Ligand binding  changes conformation of receptor
Unassociated G-protein binds to the receptor 
bound GDP molecule is phosphorylated to GTP
GDP is exchanged for GTP
G-protein dissociates into two active components:
-subunit- a
 subunit- by
 bind to their target proteins (both act as distinct second messengers)
Internal GTPase activity on -subunit dephosphorylates GTP  GDP- when ligand dissociates from receptor
-subunit dissociates from target protein  inactive again
Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins
Ga and Gby subunits re-associate and are once again available to the receptor.

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13
Q

Why is GDP exchanged for GTP

A

It is not energetically favourable for the GDP to be bound to the target protein.

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14
Q

Describe the variation in the G alpha subunits

A

There is significant variation between the G alpha subunits, separated into 3 categories which are associated with alternative signal transduction pathways. The Gby subunit is also physiologically active.

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15
Q

Describe the three different types of Ga subunits

A
Subunit: Gaq
2nd messenger: Phospholipase
Downstream effect i: PIP2 hydrolysed into IP3 and DAG
Downstream effect 2: IP3 promotes Ca2+ release from intracellular stores, DAG activates non-selective ion channels
Example:  AT-1 angiotensin receptor
Effect: vasoconstriction
Gi protein linked receptor
Inhibits adenylyl cyclase
Reduces levels of PKA
Example: M2-muscarinic receptor
Effect:  heart rate
Gs protein linked receptor
Stimulates adenylyl cyclase 
Converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP)
cAMP activates protein kinase A (PKA)
Example: 1-adrenergic receptor
Effect:  heart rate
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16
Q

What is meant by phosphorylation

A

Addition of a PO4 group- carried out by kinases and activates a number of protein enzymes

17
Q

What is meant by dephosphorisation

A

Removal of a PO4 group- carried out by phosphatases, deactivates a number of protein enzymes.

18
Q

Describe the characteristics of enzyme-linked receptors

A

Transmembrane receptors that normally consist of one transmembrane domain, which has a ligand-binding domain on the outside, and specialised enzymes (tyrosine kinase) on the outside. These receptors do not ordinarily work alone and require clustering of more than one receptor protein to activate the intracellular enzyme. Once activated, the intracellular enzyme will activate a signalling cascade inside the cell.

19
Q

Describe the signal transduction pathways of enzyme-linked receptors

A

Ligand binding  receptors clustering
Receptor clustering activates enzyme activity within cytoplasmic domain
Enzymes phosphorylate receptor
Phosphorylation  binding of signalling proteins to cytoplasmic domain
These signalling proteins  recruit other signalling proteins  signal is generated within cell
The signal is terminated when a phosphatase dephosphorylates the receptor

20
Q

List examples of enzyme-linked receptors

A

Tyrosine kinase

Insulin receptor (CD220 antigen)

Ligand: Insulin
Physiological effect: Glucose uptake

ErbB receptors
Ligand: Epidermal Growth Factor, Transforming Growth Factor 
Physiological effect: Cell growth, proliferation

Guanylyl-cyclase linked receptors

NPRA
Ligand: Atrial/ Brain natriuretic peptide
Physiological effects: Vasodilation;  Blood pressure

Ser/Thr-kinase linked receptors

TR1
Ligand: Transforming growth factor beta
Physiological effect: Apoptosis

21
Q

Describe how steroid hormones secrete their actions

A

Steroid hormones are membrane permeable (hydrophobic, lipophilic) and therefore excrete their actions on intracellular receptors. IC receptors are essentially transcription factors and hence regulate mRNA and transcription.

22
Q

Describe the two types of intracellular receptors for steroid hormones

A

Type 1; locates within cytosolic compartment and are associated with chaperone molecules- usually heat shock proteins. Once the hormone binds to the receptor the heat shock protein molecule dissociates allowing the hormone-receptor complex to form a homodimer with another hormone-complex receptor. The homodimer subsequently translocates to the nucleus where it binds to DNA and acts as a transcription factor.

Type 2: Located within the nucleus
Binding of hormone ligand  transcriptional regulation

23
Q

List examples of intracellular receptors

A

Type 1 - Glucocorticoid receptor
Ligands: Cortisol, corticosterone
Physiological effect:  immune response, Gluconeogenesis

Type 2 - Thyroid hormone receptor
Ligand: Thyroxine (T4), triiodothyronine (T3)
Physiological effect: Growth & development

Era, Estradiol, Cytosolic, Female sexual development