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pharmacology > Principle of Cellular physiology 2 > Flashcards

Principle of Cellular physiology 2 Flashcards

1
Q

Describe the three stages of signal transduction.

A
  1. Reception: An extracellular signal molecule activates a membrane receptor which alters intracellular molecules
  2. Transduction: transduce via a certain pathway
  3. Response: to activate a cellular response
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2
Q

What is the importance of signal transduction?

A

It converts one form of signal into a different form

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3
Q

Describe the role of the extracellular signal molecule and the intracellular molecule in signal transduction.

A
  • extracellular signal molecule = first messenger
  • intracellular molecule = second messenger system
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4
Q

What is in-between the first and second messenger systems and what is their role in signal transduction?

A
  • Membrane proteins which act as transducers - convert the message of extracellular signals into intracellular messenger molecules that trigger a response
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5
Q

State some of the target proteins and their responses.

A
  • Transport proteins: altered ion transport
  • Metabolic enzyme: altered metabolism
  • Gene regulatory protein: Altered gene expression
  • Cytoskeletal protein: Altered cell shape or movement
  • Cell cycle proteins: altered cell growth and division
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6
Q

Give examples of first messengers.

A
  • Amines e.g. epinephrine, adrenaline
  • Peptides and proteins e.g. angiotensin 2, insulin
  • Steroids e.g. hormones
  • other small molecules e.g. amino acids, ions, gases
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7
Q

What are the 4 main classes of receptors?

A
  1. Ligand-gated ion channels
  2. G-protein coupled receptors
  3. Enzyme-linked receptors
  4. nuclear receptors
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8
Q

What are the two examples of ionotropic receptors.

A
  • Nicotinic acetylcholine receptor
  • GABA receptor
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9
Q

What is an ionotropic receptors?

A
  • They form an ion channel pore
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10
Q

What is a nicotinic acetylcholine receptor?

A
  • A ligand gated ion channel that mediates effects of acetylcholine on muscle
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11
Q

Describe what occurs at a nicotinic acetylcholine receptor.

A
  • Binding of acetylcholine opens a channel and allows Na+ entry
  • Binds nicotine
  • Electrical event (inward Na+ current) triggers response
  • Calcium may also enter from this channel: leads to muscle contraction
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12
Q

What is a GABA receptor?

A
  • A receptor that is an ion channel
  • It is selective for Cl- ions
  • Naturally activated by GABA - CNS neurotransmitter
  • It is an inhibitory receptor
  • Has an important role in CNS
  • Activated by benzodiazepines
  • Activated by alcohol
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13
Q

Give an example of a metabotropic receptor

A

Muscarinic acetylcholine receptor

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14
Q

What is meant by a metabotropic?

A
  • Indirectly linked with ion channels on the plasma membrane through signal transduction pathways
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15
Q

What activates muscarinic receptors?

A

Ach

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16
Q

Describe the structure of G-protein coupled receptors.

A
  • Consist of three polypeptide chains: alpha, beta and gamma
  • The beta and gamma subunits bind tightly to each other
  • The alpha subunit has a guanine nucleotide binding site that binds GTP or GDP
  • alpha GDP has a high affinity for beta-gamma
  • alpha GTP has low affinity for beta-gamma
  • alpha-subunit can hydrolyse GTP
17
Q

Describe the G protein cycle.

A
  1. Unstimulated cell
  2. Adrenaline binding to beta-adrenoceptor
  3. Allows beta-adrenoceptor/G protein interaction
  4. Allows GDP/GTP exchange
  5. Allows alpha sub unit liberation
  6. Free alpha sub unit activates Adenyl Cyclase
  7. Unbinding of adrenaline/GTP hydrolysis
18
Q

Give three examples of physiological responses mediated by cAMP/PKA

A
  1. Kidney collecting duct - activated by vasopressin and stimulates water retention
  2. Vascular smooth muscle and cardiac muscle - activated by adrenaline and promotes relaxation/increase heart rate
  3. Liver - activated by glucagon and promotes release of glucose in the blood
19
Q

Describe the termination of the signal transduction.

A
  • cAMP is hydrolysed by phosphodiesterase (PDE)
  • When hormone is removed PDE rapidly clears cAMP from the cell
  • Protein reassembles into tetramer and are inactivated
  • PDE’s are inhibited by caffeine (explains why heart beats faster after consuming coffee)
20
Q

What is meant by desensitisation of receptor?

A

A feedback mechanism to reduce the signal transduction

21
Q

Describe the mechanism of the desensitisation of receptors.

A
  1. Protein phosphorylation leads to cellular response
  2. PKA phosphorylates beta-adrenoreceptor kinase (beta-ARK)
  3. beta-ARK phosphorylates beta-adrenoreceptor and reduces affinity for adrenaline
  4. Reduced affinity leads to reduced cellular response despite sustained stimulation.

pharmacology (40 decks)

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