6.1 Receptors in cell signalling

Question 1

Define ligand

Answer 1

small molecule bind to receptors AND activate it (agonist)

Question 2

Define antagonist

Answer 2

bind to receptor WITHOUT activating it

Question 3

Define partial agonist

Answer 3

bind to receptor but CAN’T trigger MAXIMUM response

Question 4

Define receptor

Answer 4

recognises SPECIFIC ligand, bind and regulate a cellular process

Question 5

what are acceptors?

Answer 5

basic receptors which can carry out their function WITHOUT a ligand
should a ligand bind, their basic function will be altered (hyper / hypo sensitive)
e.g. dihydrofolate reductase

Question 6

Describe specificity of response through hydrophilic and hydrophobic signalling molecule

Answer 6

hydrophilic: bind to receptor on extracellular face of cell surface, activating a cellular process
hydrophobic: diffuse through lipid bilayer, bind to SPECIFIC receptor within the cytoplasm / nucleus, altering the rate of cell transcription

Question 7

Describe the role of receptors in cellular physiology

Answer 7

1. hormones / local chemical mediators
2. Ca2+ release - muscle contraction (IP3 / RyR)
3. neurotransmission - neurones (ACh bind to AChR)
4. control gene expression - steroids
5. immunity - antibodies bind to antigen

Question 8

Mechanisms to transduce extracellular hydrophilic signal into intracellular event

Answer 8

all receptors on membrane - hydrophilic

1. receptor with COUPLED EFFECTOR e.g. GPCR
2. receptor with integral ENZYME - enzyme activated when bound
3. receptor with integral ION CHANNEL - receptor is ion channel

Question 9

similarities between receptor binding sites and enzymes

Answer 9

1. SPECIFICITY both receptor and substrate
2. binding is often REVERSIBLE
3. LIGAND / ALLOSTERIC regulation binding to receptor can often cause CONFORMATIONAL change in receptor

Question 10

difference between receptor binding and enzyme

Answer 10

1. ligand binding has a HIGHER AFFINITY than enzyme

2. substrate bound to enzyme active site causes modification that is catalysed BY the active site

Question 11

how can you classify receptors?

Answer 11

by how well they bind to agonist - AFFINITY

and how much response is caused by agonist - activated

Question 12

Describe the mechanism employed by intracellular receptors involved in cellular signalling via hormones

Answer 12

1. hormone diffuses across the lipid bilayer to binds to the hormone receptor site on the DNA binding domain
2. binding of hormone to receptor causes the INHIBITORY PROTEIN complex to leave the DNA binding domain
3. the DNA binding site is now exposed and (RNA polymerase can enter) and alter the rate of transcription

Question 13

Describe the mechanism employed by membrane bound receptors with integral enzyme activity involved in cellular signalling via hormones

Answer 13

e.g. insulin receptors, growth factor receptors
tyrosine kinase-linked receptors
1. binding of hormone to extracellular sites activates protein kinase activity in the cytoplasm, causing it to autophosphorylate
2. phosphorylated tyrosine residues are recognised by transducing proteins / enzymes (with phosphotyrosine recognition sites)
3. association of protein / enzyme to tyrosine causes the enzymes to become allosterically activated, transducing message to intracellular chemical event

Question 14

Describe the mechanism employed by the membrane- bound receptors with integral ion channels involved in cellular signalling via local mediator & neurotransmitter

Answer 14

1. agonist binds to ligand bated ion channel
2. causes change in conformation and opening of gated channel
3. ions flow down electrochemical gradient
   transduces signal into electrical event at plasma membrane

Question 15

Describe the mechanism employed by the membrane-bound receptor with no integral enzyme / channel activity involved in cellular signalling via local mediators / neurotransmitters

Answer 15

e. g. mAChR, adrenoceptors, dopamine: all G-protein-coupled receptor
1. ligand binds to binding domain on the 7 transmembrane domain receptor coupled to G-protein using GTP (which goes to effector)
2. binding of receptor results in conformational change, activating GDP/GTP exchange in G-protein
3. transducing message onto enzyme / channel in membrane

Question 16

Describe amplification

Answer 16

small amounts of ligand required to evoke a large response
cascade - can produce further amplification
1 enzyme can activate many substrates

Question 17

Describe the structure of GPCR

Answer 17

has 7 transmembrane domain, containing the ligand binding site

Question 18

Describe the structure of a classical ligand-gated ion channel

Answer 18

1 peptide with 5 subunits, each with 4 transmembrane domains
2nd of 4 transmembrane domain (M2) interact with ion ‘pore’
only 2 of the 5 subunits have binding domain (on N terminal)
forming both sides of the pore
e.g. GABA receptor, glycine receptor

Question 19

Discuss the principles of communication between cells via chemical messengers in the paracrine, endocrine & nervous system

Answer 19

paracrine: local chemical mediators affecting adjacent cells of the same tissue
Endocrine: hormone signalling to different cells via circulation
Nervous system: neurotransmitters at specialised cell junctions in nervous systems (synapse)

Question 20

Describe the structure of the non-classical ligand-gated ion channel

Answer 20

opened via the binding of ATP: ATP-sensitive K+ channel
closed via binding of ATP: K+ channels in maintaining depolarisation (?)
ryanodine receptor: binding of Ca2+ causes more Ca2+ to enter

Question 21

Describe the structure of Na+/Ca2+ channels

Answer 21

1 peptide, 4 subunits, 6 transmembrane domains, 4th senses changes in voltage

Question 22

describe the structure of K+ channels

Answer 22

similar to Na+ / Ca2+, but 4 subunits, each form 1/4 of the pore, so come together to form the K+ pore