Lecture 11- Biological signalling and receptors

Question 1

define receptor

Answer 1

a molecule that recognises specifically a molecule (ligand) or family of molecules which in response to ligand binding brings about regulation of a cellular process

Question 2

receptors in an unbound state

Answer 2

functionally silent

Question 3

role of receptors

Answer 3

• Neurotransmission - cellular deliver - control of gene expression - signalling by hormones - cell adhesion - modulation of the immune response - sorting of intracellular proteins - release off intracellular calcium stores

Question 4

two main type of receptors

Answer 4

cell surface intracellular

Question 5

cell surface receptors

Answer 5

tyrosine kinase GPCR Ligand gated Voltage gated

Question 6

intracellular

Answer 6

nuclear e.g. steroids

Question 7

ligand

Answer 7

any molecule which binds specifically to a receptor site

Question 8

agonist

Answer 8

• May produce activation of a receptor

Question 9

antagonist

Answer 9

• Oppose the action of agonist activation

Question 10

signalling between cells via 92)

Answer 10

-secreted molecules - plasma membrane bound molecules (APCs)

Question 11

types of signalling via secrete molecules

Answer 11

paracrine endocrine synaptic

Question 12

paracrine

Answer 12

• Signalling molecule secreted into tissue and acts on adjacent cells • Local signal

Question 13

endocrine

Answer 13

• If signalling molecule travels around the circulation to find target cell in different tissue • E.g. hormones

Question 14

synaptic

Answer 14

• NT released in the junction b/w 2 nerve cells • E.g. NMJ

Question 15

three main types of chemical signalling

Answer 15

• Local chemical mediators • Hormones • NT

Question 16

difference between receptors and acceptors

Answer 16

Receptors are silent at rest, whilst acceptors operate in the absence of ligand/ Agonist binding to the receptor will stimulate biological response, whilst in acceptors, binding alone produces no response

Question 17

affinity in enzymes

Answer 17

km

Question 18

affinity in receptors

Answer 18

Kd

Question 19

affinity of ligand binding at receptor site is generally much …… than binding of substrate and allosteric regulators to enzyme site

Answer 19

higher

Question 20

receptors are classified according to

Answer 20

1) the agonist it recognises 2) affinity of a series of agonists 3) affinity of antagonists

Question 21

affinity of a series of agonists e.g…

Answer 21

i. Nicotinic- higher affinity to nicotine ii. Muscarinic- higher affinity to muscarine

Question 22

affinity of antagonists e.g..

Answer 22

• M1- antagonist= pirenzipine • M2- antagonist= gallamine • M3- antagonist= hexahydrosilodiphenol

Question 23

the agonist it recognises e.g.

Answer 23

adrenoreceptors

Question 24

types of receptors (4)

Answer 24

1. Membrane-bound receptors with integral ion channel o Ligand-gated nAChR 2. Membrane-bound receptors with integral enzyme activity o GPCR- adrenaline 3. Membrane bound receptors which couple to effectors through transducing proteins o Tyrosine kinase- insulin 4. Intracellular receptors o Steroid receptors- oestrogen

Question 25

Membrane-bound receptors with integral ion channel e.g.

Answer 25

o Ligand-gated nAChR

Question 26

Membrane-bound receptors with integral enzyme activity

Answer 26

o GPCR- adrenaline

Question 27

Membrane bound receptors which couple to effectors through transducing proteins

Answer 27

o Tyrosine kinase- insulin

Question 28

Intracellular receptors

Answer 28

o Steroid receptors- oestrogen

Question 29

receptors on the cell surface for

Answer 29

hydrophilic signalling molecules

Question 30

receptors within the cell for

Answer 30

hydrophobic signalling molecules

Question 31

steroids can pass the lipid bilayer due to being

Answer 31

hydrophobic and small

Question 32

hydrophobic is used interchangeable with

Answer 32

lipophilic- will pass the membrane

Question 33

polar molecules

Answer 33

will not pass the membrane

Question 34

how are steroid transported

Answer 34

through the bloods on proteins such as albumin

Question 35

where are steroidal receptors

Answer 35

int he cytoplasm or nucleus

Question 36

steroids work to

Answer 36

activate or inhibit the expression of genes

Question 37

classical ligand gated ion channel

Answer 37

- nAChR- gated Na+, K+, Ca2+ channel - Gaba receptor- gated chloride channel - Glycine receptor- gated chloride channel - Glutamate receptor- gated entry of Ca2+

Question 38

nicotinic acetylcholine receptor

Answer 38

- Fastest mode of transport into the cell - Ligand-gated receptor (all have a pentameric structure)

Question 39

structure of nicotinic acetylcholine receptor

Answer 39

Pentameric- 2 subunits related to ACH binding- all subunits involved in resting pore

Question 40

outline how nicotinic acetylcholine receptor causes influx of sodium and depolarisation

Answer 40

1) ACh binds to the receptor 2) Causes the gate to open 3) Na+ can flood into cell and cause depolarisation of end plate

Question 41

non classical ligand gated ion channels

Answer 41

- ATP-sensitive K+ channel - Ryanodine receptor (calcium)

Question 42

example of a membrane bound receptor with integral enzyme activity

Answer 42

signalling via Tyrosine Kinases

Question 43

tyrosine kinases receptors work as

Answer 43

dimers

Question 44

outline how TKs cause cellular signalling

Answer 44

- Dimerization causes autophosphorylation of tyrosine residues on the inside of the channel—\> 2nd messenger signalling - Receptors generally work via transducer proteins o Transducer phosphorylation by tyrosine residues o Transducer binds target enzyme and activates

Question 45

example of Tyrosine kinase receptros

Answer 45

growth factor receptors ANP receptors

Question 46

ANP receptors

Answer 46

linked directly to guanylyl cyclase

Question 47

growth factor receptors (TK)

Answer 47

linked directly to tyrosine kinase

Question 48

give example of ligand of growth facotor receptor ligands

Answer 48

insulin epidermal growth factor (EGF) platelet derived growth factor (PDGF)

Question 49

When the tyrosine residues are phosphorylated

Answer 49

enzymes (transducers) recongise the complex due to SH2 domain. - Example transducers: IRS-1, Grb2

Question 50

when insulin binds to its TK receptor

Answer 50

- Insulin binds to the insulin binding domain on the extracellular region of the tyrosine kinase receptor - This causes a conformational change in the receptor- dimerization - Dimerization causes autophosphorylation of tyrosine kinase domain on the inner part of the receptor - Phosphorylated TKs attract transducers o Overall will cause increased transcription of DNA o Increased number of GLUT4 channels

Question 51

structure of insulin receptor

Answer 51

made up of alpha and beta change linked by disulphide bridge - 2 binding domains - 1 transmembrane domain - 2 tyrosine kinase domains

Question 52

Membrane bound receptors which couple to effectors through transducing proteins e.g.

Answer 52

G-protein couple receptors

Question 53

G-protein couple receptors are the

Answer 53

biggest class of receptors

Question 54

structure of GPCR

Answer 54

- 7 transmembrane domain receptors - Coupled through GTP-binding regulatory protons (G-proteins) to enzymes or channels

Question 55

G protein is composed of

Answer 55

three subunits: ◦Alpha ◦Beta ◦Gama

Question 56

example of adrenaline binding to GPCR

Answer 56

• In resting state GDP is bound to the G-protein • Adrenaline comes along and binds causing a confirmation change in receptor • GDP is released from alpha subunit of G-protein • GTP is able to bind to the g-protein • G-protein dissociates • G-protein activates effector • Effector (AC) converts ATP to cAMP (Gs)

Question 57

how does the steroid receptor work

Answer 57

• Receptors held in silent state by inhibitory protein complex - blocks DNA binding site • When a steroid hormones binds the inhibitory protein is released and the DNA binding site is free

Question 58

responses to receptor activation can lead to both

Answer 58

cellular activation or inhibition depdneing on the type of receptoer activated

Question 59

amplification in cellular signalling

Answer 59

binding of a signal ligand to a receptor, can cause a huge reaction within a cell e.g. * Activated G-protein (with GTP attached) activates effector enzyme ((AC) * AC causes ATP--\> AMP * CAMP activates protein kinases * Protein kinase phosphorylates thousands of enzymes * Product of enzyme