Lecture 2 Part 2

4 Types of Receptors

  • Four main types of receptors will be discussed:

    1. Ion Channels

    2. G Protein-Coupled Receptors (GPCRs) — mediate transport of neurotransmitters

    3. Tyrosine Kinase Coupled Receptors

    4. Intracellular Receptors


RYR1 & Genetic Variation & Risk of Malignant Hyperthermia

  • Genetic variation in RYR1 — target for differnt anesthetic agents > can increase risk of developing malignant hyperthermia

  • Malignant hyperthermia — severe reaction to anesthetic agents — e.g. volatile anesthetics & muscle relaxants

  • Individuals that have a particular genetic mutation in RYR1 > more prone to developing malignant hyperthermia


Ivacaftor for the Treatment of Cystic Fibrosis Targets a Specific Variant G551D-CFTR

  • Ivafactor > reverses the effects of genetic mutation > enables Cl to move through the channel > no build-up of mucosal layer > complete remission of symptoms

G Protein-Coupled Receptors (GPCRs) — E.g. Adrenergic Receptors

  • Alpha 1 & alpha 2 G-protein coupled receptor (Ga1 & Ga2)> mediate smooth muscle contraction

  • Beta G-protein coupled receptor (Gb) > alter heart muscle contraction & smooth muscle relaxation

  • Depending on which G-protein coupled receptor the drug molecule binds, it will mediate a different response


Slide 15

  • People that have normal functioning beta-2 adronergic receptor > respond well to bronchodilators > respond well to asthma medication

  • People that have lost functioning beta-2 adrenergic receptors > don’t respond well to bronchodilators > don’t respond well to asthma medication

Frequency of SNPs

  • Glycine change — more common


Another SNP

  • Gly49 carriers don’t get as much bnefit from their beta-blocker > increased risk of developing secondary cardiovascular event

  • This is a loss of function mutation > reduce the response to either asthmatic medication or beta blcokers


Effect of Gnenetic Variants in Opioid Receptors

  • 3 genetic variations exist in mu opioid receptors impacting pain management


Protein Phosphorylation

  • Overexpression of these types of receptors is associated with cancers > modulate cell proliferation


Examples of Drugs that Target Estrogen Receptor — Tamoxifen

  • Genetic variation in CYP2D6 > impact the amount of endoxifen that binds to estrogen receptor

  • Genetic variation in estrogen receptor > also alter response of endoxifen binding to this receptor

  • Example of how drug variation in drug metabolising enzymes can alter the amount of endoxifen formed & how genetic variation in a receptor can alter the potency of endoxifen to halt the progression of breast cancer