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ESA 1 - ICPP > Signalling Molecules > Flashcards

Signalling Molecules Flashcards

1
Q

What does the term ‘pharmacology’ mean?

A

Study of molecular signals regulating physiological processes.

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2
Q

What are the different types of extracellular signals (based on distance of action)?

A
  1. Autocrine
  2. Paracrine
  3. Endocrine
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3
Q

What is autocrine signalling?

A
  • Cells respond to signalling molecules they produce and release themselves.
  • Typically act over microns.
  • Shares many paracrine signalling molecules, e.g. Cytokines and growth factors.
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4
Q

What is paracrine signalling?

A
  • Act on neighbouring cells - molecules released into extracellular environment and induce changes in receptor cells.
  • Uses signals such as:
    1. Neurotransmitters
    2. Local chemical mediators
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5
Q

What is the function of neurotransmitters?

A
  • Mediate signalling between neurons over synapses (20 nm distance, msecs transmission velocity).
  • Electrochemical system as enables chemical signal conversion/coupling with electrical signals.
  • Signalling can be:
    1. Excitatory - increases firing rate post-synaptically
    2. Inhibitory - decreases firing rate post-synaptically
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6
Q

What are the major groups of neurotransmitters?

A
  1. Amino acids
    • glutamate
    • glycine
    • GABA
  2. Monoamines
    • adrenaline
    • noradrenaline
    • dopamine
    • serotonin
  3. (Neuro)peptides
  4. Acetylcholine
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7
Q

Name examples of inhibitory neurotransmitters.

A
  • GABA
  • Glycine
  • Dopamine
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8
Q

Name examples of excitatory neurotransmitters.

A
  • Acetylcholine
  • Adrenaline
  • Noradrenaline
  • Dopamine
  • Serotonin
  • Glutamate
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9
Q

When are local chemical mediators used in signalling?

A

Local injury results in local signalling response - paracrine: rapid, focused and integrated.

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10
Q

Give examples of local chemical mediators.

A
  • Cytokines (interleukins, chemokines, interferons, histamine)
  • Eicosanoids (prostaglandins, leukotrienes)
  • Others: nitric oxide, neuropeptides, platelet-activating factor
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11
Q

Give examples of therapeutic applications of pharmaceutical derivates of NTs.

A
  • Propranolol antagonises adrenaline/noradrenaline: treatment of hypertension, thyrotoxicosis, etc.
  • Dopamine precursors + agents to inhibit breakdown: treatment of parkinsonism
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12
Q

Give examples of therapeutic applications of pharmaceutical derivates of local chemical mediators.

A
  • Inflammation: steroids are potent blockers of inflammatory signal of local mediators.
  • Moderate pain: non-steroidal anti-inflammatories (NSAIDs) block local mediator pain signal.
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13
Q

What is endocrine signalling?

A
  • Glands produce hormone signalling molecules - typically act over long distances/throughout whole body via bloodstream.
  • Molecules are highly potent - picomolar to nanomolar range, with timescale of action ranging from seconds to months.
  • Recipient cells need to express receptors.
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14
Q

Give examples of the therapeutic applications of exogenous endocrine analogues.

A
  • Adrenaline i.v. Use in A&E
  • Insulin derivates for blood sugar control in diabetes
  • Steroid use as anti-inflammatories
  • Steroids in contraception
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15
Q

What are the major types of hormones?

A
  1. Catecholamines
    • adrenaline
    • noradrenaline
    • dopamine
  2. Peptides and proteins
    • insulin
    • atrial natriuretic peptide (ANP)
    • oxytocin
  3. Steroids
    • testosterone
    • progesterone
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16
Q

What are catecholamine hormones, what is their mode of action and what is their plasma 1/2 life?

A
  • Tyrosine derivatives
  • Hydrophilic, receptors in PM
  • Mode of action (msec-sec)
    1. Change in membrane potential
    2. Trigger synthesis of cytosolic second messengers
  • Plasma 1/2 life = seconds
17
Q

What are peptide/protein hormones, what is their mode of action and what is their plasma 1/2 life?

A
  • Short to long chain of amino acids.
  • Hydrophilic, receptors in PM
  • Mode of action (min-hrs):
    1. Trigger synthesis of cytosolic 2nd messengers
    2. Trigger protein kinase activity
  • Plasma 1/2 life = minutes
18
Q

What are steroid hormones, what is their mode of action and what is their plasma 1/2 life?

A
  • Derived from cholesterol lipid.
  • Lipophilic, intracellular receptors (cytosolic or nuclear)
  • Mode of action (hrs-days):
    1. Receptor-hormone complex controls transcription and stability of mRNA.
  • Plasma 1/2 life = hours
19
Q

What are the main types of drug targets, and what is the main exception?

A 
- RITE:
   ~ Receptors
   ~ Ion channels
   ~ Transporters
   ~ Enzymes
- In chemotherapy/antibiotics, drug target is often a structural protein or DNA.
20
Q

What are the different types of receptors targeted by signalling molecules?

A 
- KING:
   ~ Kinase-linked
   ~ Ion channels (ligand-gated) - ionotropic Rs
   ~ Nuclear/intracellular
   ~ G-protein coupled - metabotropic Rs
21
Q

What is the MOA of kinase-linked receptors and give examples?

A
  • Act via protein phosphorylation - causes signalling cascade of molecular switches - regulation of gene transcription.
  • Takes hours.
  • Mediate signals from a wide variety of protein molecules.
  • E.g. Cytokinesis receptors
22
Q

What is the MOA of ionotropic receptors and give examples?

A
  • Ligand (e.g. ACh) binding causes ion channel protein to open, allows transmembrane movement of ions - ion currents and voltage change modulates AP generation in neurones and contraction in muscles.
  • Coupled to Ca2+ signalling.
  • Acts in milliseconds.
  • E.g. Nicotinic ACh R.
23
Q

What is the MOA of nuclear/intracellular receptors and give examples?

A
  • Lipid-soluble ligand (steroids, thyroid hormone, vitD) binds to intracellular receptor and complex migrates to nucleus - binds to a gene TF - activates/inactivates gene(s).
  • Takes hours.
  • E.g. Oestrogen R.
24
Q

What is the MOA of metabotropic receptors and give examples?

A
  • 3 major types: Gs, Gi, Gq - activate different intracellular signalling routes via 2nd messengers, e.g. Ca2+ release, protein phosphorylation. Or allow ion channel to open - change in excitability.
  • Act in seconds.
  • E.g. Muscarinic ACh R.

ESA 1 - ICPP (18 decks)

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