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Intermediate Pharmacology (PHAR0009) Notes - Receptors and Signalling 7,92 €
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  3. University College London (UCL)
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  5. Intermediate Pharmacology (PHAR0009)

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Intermediate Pharmacology (PHAR0009) Notes - Receptors and Signalling
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  • Grado
  • Intermediate Pharmacology (PHAR0009)
  • Institución
  • University College London (UCL)

Explore Intermediate Pharmacology at UCL with a focus on the Receptors and Signalling chapter. Delve into the realm of agonists, drugs, and the intricate structure of receptors. Unravel the complexities of cellular signaling and signal transduction. Please note that these materials are intended for...

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Información del documento

  • 1 de diciembre de 2023
  • 14
  • 2021/2022
  • Notas de lectura
  • Dr talvinder sihra
  • Todas las clases

Temas

  • agonists
  • drugs
  • receptor structure
  • receptors
  • signalling
  • signal transduction

Escuela, estudio y materia

  • University College London (UCL)
  • Desconocido
  • Intermediate Pharmacology (PHAR0009)
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Receptors and Signalling – Summary
Introduction
 Pharmacology – the study of drugs
o Naming of drugs + targets of drug action + selectivity of drugs + measuring ratio of beneficial to
unwanted effects
 Naming drugs
o Classification according to:
 Therapeutic use
 Molecular mechanism of action
 Chemical structure
o Approved name + brand name
 Targets of drug action
o Selective toxicity
 Drugs bind to other sites of action in addition to main site  resulting in unwanted effects
o Magic bullet
 Drug might act selectively at intended site of action
 Has high affinity for cell – only targets main site by aiming with specific chemicals
 Has little effect for organism – minimising damage
 Selectivity of drugs
o Pharmacokinetics – drug motion
 Study of time course of drug absorption + distribution + metabolism + excretion
 Aim to achieve a higher concentration of drug at desired site of action
o Pharmacodynamics – drug power
 Study of biochemical and physiological effects of drugs
 Design drug to have a higher affinity for desired site of action
o Drug targets
 Action at a specific binding site
 Specific macromolecular targets may have high affinity for drug + high specificity –
due to stereochemistry of substrate cofactor binding
o Hormone / neurotransmitter receptors – antagonists or agonists
o Enzymes
o Transporters
o Ion channels
o DNA
 Action not involving a specific binding site
 Drug without identifiable binding site – acts at higher concentrations
o Action of drug is less affected by changes in chemical structure
 Measuring ratio of beneficial to unwanted effects of drugs
o Amount of risk acceptable – influenced by severity of medical condition
o Ehrlick’s therapeutic index
 Ehrlick’s therapeutic index = maximum non-toxic dose / minimum effective dose
 Has difficulties with measurements – due to individual variations to drug
o Therapeutic index – uses better defined doses producing effects in
50% of subjects
 Therapeutic index = TD50 / ED50 = toxic dose / effective dose
 Dose response curve
o Toxicity
 In animal studies – death can be used as a measure of
toxicity
 Therapeutic index = LD50 / ED50 = lethal dose / effective dose

, Receptors and Signalling – Summary
Receptor Structure
 Receptors = protein involved in mediating the effects of intercellular signalling molecules
o Site of action of: neurotransmitters + hormones + growth factors + other intercellular signalling
molecules
o Four structurally distinct families
 Transmembrane receptors
 Ligand-gated ion channels (LGICs)
 G-protein-coupled receptors (GPCRs)
 Kinase-linked and related receptors
 Intracellular receptors
 Nuclear receptors

Ligand-Gated Ion Channels – LGICs
 Ligand-gated ion channels – AKA
o Agonist-activated ion channels
o Neurotransmitter-gated ion channels
o Ionotropic receptors
 Structure
o Multi-subunit (oligomeric) transmembrane proteins – contain a central integral ion channel
 Multiple subunits co-assemble with each other  forming a ring-like structure
 Pentameric – 5 complexes
o nAChRs
o GABAARs
o GlyRs
o 5-HT3Rs
 Tetrameric – 4 complexes
o GluRs
 Trimeric – 3 complexes
o ATP(P2X)Rs
o Extracellular agonist binding site – linked by conformational change to narrow portion of channel
located within lipid bilayer = channel gate
o Neurotransmitter bind to site on extracellular domain  causing conformational change  opening
integral ion channel (excitatory or inhibitory)
 Cation channel = excitatory – causes membrane depolarisation
 Acetylcholine (ACh)
o Nicotinic acetylcholine receptor (nAChR)
 5-hydroxytryptpamine (5-HT)
o 5-HT(serotonin) type 3 receptor (5-HT3R)
 Glutamate (Glu)
o Glutamate receptor (GluR)
 Adenosine triphosphate (ATP)
o ATP (P2X) receptor
 Anion channel = inhibitory – causes membrane hyperpolarisation
 g-aminobutyric acid (GABA)
o GABAA receptor (GABAAR)
 Glycine (Gly)
o Glycine receptor (GluR)
o Subunit structure
 Pentameric LGICs
 Each of the 5 subunits are a single polypeptide

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