Cell receptors Flashcards

1
Q

What are cell receptors (5)

A
  1. Membrane-bound or intracellular
  2. Protein molecules that communicate signals
  3. Activated by molecules known as ligands
  4. Distribution and concentration vary in different tissues/organs.
  5. Therapeutic targets
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2
Q

How does receptor activation work (7)

A
  1. Lock and key hypothesis” – based on structural similarity
  2. Key = ligand
  3. Lock = receptor
  4. correct fit = receptor activation
  5. incorrect fit = no receptor activation
  6. Chemical interactions occur between receptor and ligand
  7. SPECIFICITY and SELECTIVITY of ligand-receptor interactions
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3
Q

What are the chemical interactions between ligand and receptor (4)

A
  1. Electrostatic interactions
  2. Hydrophobic interactions
  3. Stereospecific interactions
  4. Covalent bonds
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4
Q

What are the main types of receptors (5)

A
  1. G-protein coupled receptors
  2. Tyrosine kinase receptors
  3. Nuclear receptors
  4. Ligand-gated ion channels
  5. Voltage-gated ion channels
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5
Q

What are G-protein coupled receptors (GPCR) and an example (5)

A
  1. Trans-membrane and integral membrane proteins
  2. Receptor coupled with a G-protein
  3. Wide variety of different GPCRs binding a range of ligands
  4. Ligands bind to extracellular domains, and signal transduction is activated intracellularly.
  5. Example: beta2-adrenoceptors
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6
Q

What are G-proteins (3)

A
  1. guanine nucleotide-binding regulatory protein
  2. Signal transducer – from receptor to effector
  3. Heterotrimer (alpha, beta, gamma subunits)
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7
Q

What are G-protein regulated effectors (2)

A
  1. Enzymes (e.g. adenylyl cyclase, phospholipase C and cGMP phosphodiesterase)
  2. Some ion channels
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8
Q

What are examples of an inactive and active G-protein (3)

A
  1. Inactive G-protein = alpha-GDPbeta-gamma
  2. Active G-protein = alpha-GTPbeta-gamma
  3. The affinity of the alpha subunit changes with ligand-GPCR binding.
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9
Q

What are second messengers (4)

A
  1. Small molecules
  2. Formed in response to the activation of some receptors
  3. Example includes: Cyclic nucleotides (cAMP) (via Adenylyl cyclase)
  4. Receptor agonist = First messenger
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10
Q

What are tyrosine-kinase receptors and what is an example (5)

A
  1. Trans-membrane proteins (two monomer units dimerise)
  2. Contain enzyme activity within receptor proteins – tyrosine kinases
  3. Monomers within the dimer cross-phosphorylate
  4. signals intermediary signalling proteins that activate signalling pathways
  5. Example: Insulin receptor
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11
Q

How do tyrosine-kinase receptors work (3)

A
  1. Activated receptor can accept phosphate groups from ATP to form ADP
  2. Intermediate proteins can obtain a phosphate group from the activated tyrosine-kinase receptor which in turn activates the intermediate receptor
  3. This triggers a ‘phosphorylation cascade’ resulting in a cellular response (via regulation of gene expression)
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12
Q

What are nuclear receptors and an example (4)

A
  1. Intracellular receptors
  2. Agonists enter the cell – lipid soluble
  3. The ligand-receptor complex enters the nucleus and alters gene expression
  4. Example: steroid receptors
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13
Q

What are ion-channel receptors (7)

A
  1. Ligand-gated AND Voltage-gated receptors
  2. Receptor and effector (ion channel) are part of the same transmembrane protein
  3. Binding of agonist results in the opening on the ion channel → membrane depolarisation
  4. Fast responding – in excitable cells
  5. Selective for which ions they allow to cross the membrane (Na+, Ca2+, K+, Cl-)
  6. Rely on there being a concentration gradient of the particular ion across the membrane.
  7. At rest there is ~ -70mV charge across the cell membrane
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14
Q

How do ligand-gated receptors work and what is an example (3)

A
  1. The opening of the ion channel is dependant on the appropriate ligand binding
  2. Ligand binding can occur extracellularly (first messengers) or intracellularly (second messengers)
  3. Example: nicotinic Acetylcholine receptor (nAChR)
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15
Q

How do voltage-gated receptors work and what is an example (4)

A
  1. The opening of the ion channel is dependant on the change in the cell membrane potential
  2. Size of depolarisation affects which voltage-gated channels open
  3. Go through a refractory phase **post re-closing
  4. Example: L-type Ca2+ channel
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16
Q

What is Desensitation, tachyphylaxis and tolerance (3)

A
  • Desensitisation = when the biological response of a receptor to its agonist diminishes when it is continuously or repeatedly exposed to the agonist
  • Tachyphylaxis = desensitisation that occurs very rapidly
  • Tolerance = a more gradual loss of response of the receptor to its agonist
17
Q

How are receptors used as therapeutic targets (6)

A
  1. Attractive targets for therapeutic compounds (drugs)
  2. Importance of the chemistry and pharmaceutics (formulation) of drug effect
  3. Issues of distribution of receptors
  4. Specificity vs selectivity of drugs
  5. Concept of adverse drug reactions and side effects
  6. Necessary to consider the entire ‘signal chain’ and not specific receptor as therapeutic target