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3. ICPP > 1.2 RITE KING > Flashcards

1.2 RITE KING Flashcards

1
Q

What is extracellular signalling?

A

Two or more parts of a system, communicating and working in synchrony with a shared common purpose

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2
Q

Extracellular signalling - explain endocrine signalling. Answer the following questions:

How does it work?
Secreted where?
Potency?
Timescale? 
Extra info
Clinical relevance
A
  1. Glands/tissues produce hormones that act as signalling molecules with many specific target types
  2. Secreted into blood stream (therefore travel large distances)
  3. Highly potent
  4. Seconds to months depending on molecule
  6. Exogenous endocrine molecules mimic endogenous e.g. Adrenaline IV, insulin derivative controls blood sugar
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3
Q

Three types of endocrine molecule?

Answer the following questions for each:
Solubility 
Time course of action
Receptor location
Mechanism 
Example (optional - just for context!)
A
  1. Catecholamines (amine/amino acid derivative)
    - hydrophilic
    - time course of action is milliseconds to seconds
    - receptor is plasma membrane
    - causes change in membrane potential, triggers synthesis of cytosolic second messengers.
    - adrenaline/dopamine
  2. Peptides and proteins
    - hydrophilic
    - minutes to hours
    - plasma membrane
    - triggers synthesis of cytosolic second messengers, triggers protein kinase activity (modifies other proteins chemically adding phosphate)
    - insulin allowing control of blood sugar
  3. Steroids
    - lipophilic
    - hours to days
    - cytosolic or nuclear
    - receptor-hormone complex controls transcription and stability of mRNAs
    - glucocorticoid/mineralocorticoids
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4
Q

What are glucocorticoids and mineralocorticoids?

A

ACTH produced from pituitary gland, goes to Adrenal glands, stimulate release of cortisol (long term effects)

Gluco- proteins and fats converted into glucose inc blood sugar
Mineral- retention of sodium and water by kidney inc blood vol and bp

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5
Q

How do paracrine molecules work? Give examples and their functions.

A

Molecules released into extracellular environment, signalling nearby cells.

E.g. Neurotransmitters - chemical signal converted to electrical
Excitatory NT - increase action potential firing
Inhibitory NT - decrease

  • acetylcholine - excitatory at end organ
  • monoamines - adrenaline (E) , noradrenaline (E) , dopamine (E/I), serotonin (E)
  • AA - glutamate (E), glycine (I), GABA (I)

-cytokines, chemokines, interferons, histamine for local injury!

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6
Q

Therapeutic application of paracrine neurotransmitter molecules? (3)

A

Hypertension - Propanolol antagonises (nor)adrenaline
Parkinson’s - dopamine precursors given to inhibit its breakdown
Pain - NSAIDS block local mediator pain signal

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7
Q

What is autocrine extracellular signalling?

A
  1. Cells respond to molecules they release themselves

2. Shares many paracrine signalling molecules e.g. Cytokines + growth factors

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8
Q

What are the main drug targets?

A

Receptors
Ions
Transporters
Enzymes

RITE

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9
Q

What are the main types of Receptors?

A

Kinase Linked receptor
Ionotropic receptor/ion channels ligand gated
Nuclear/intracellular
G-protein coupled receptors

KING

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10
Q

What is a kinase linked receptor?

A
  1. Type of drug target receptor
  2. Act via phosphorylation and sets signalling cascades often leading to gene transcription
  3. E.g. Cytokines, hormones, growth factors
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11
Q

What is an ionotropic receptor?

A
  1. Type of drug target receptor
  2. Allow ion current across membrane and regulates voltage change, action potential
  3. E.g neurons, muscle contraction
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12
Q

What is a nuclear/intracellular receptor?

A
  1. Type of drug target receptor
  2. Ligand receptor complexes migrate to nucleus and activate/inactivate genes to regulate up/down
  3. Need to be lipid soluble
  4. E.g. Steroids, thyroid hormone, vit D
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13
Q

What is a G-protein coupled receptor?

A
  1. Type of drug target receptor
  2. Gs, Gi, Gq activates intracellular signalling routes
  3. E.g. Serotonin/dopamine
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14
Q

Ions are a type of drug target, explain how.

A
  1. Selectively allow ion current to flow across plasma membrane (Na+, K+, Ca2+, Cl-)
  2. Ligand, voltage gated
  3. Modulated by GPCR activity
  4. Morphine via GPCR activation. Inhibits Ca2+ driven transmitter release, increases hyperpolarisation K+ current reducing pain
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15
Q

Transporters are a type of drug target, how do they work?

A
  1. Transport of ions/molecules by facilitated diffusion - use ATP
  2. Neurotransmitter re-uptake
  3. SSRIs fluoxetine used to stop serotonin being re-uptaken - antidepressant effect
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16
Q

Enzymes are a type of drug target, how do they work?

A
  1. Signal processing transformation synthesis degradation
  2. Competitive inhibition
  3. Increased levels of precursor substrate

3. ICPP (15 decks)

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