Drug Action + Cell Signaling Flashcards
Targets of drug action
Receptors, ion channels, enzyme and carrier molecules (eg transporter proteins)
Receptor - agonist direct changes
Opening/closing ion channels
Agonist-receptor Transduction Mechanisms Changes
enzyme activation/inhibition, ion channel modulation and DNA transcription
Antagonist-Receptor Changes
Nothing
3 types of receptors
cell surface (gives fastest response), intracellular receptors and organelle/nuclear receptors (slowest response)
Ion Channels Outline
Contain ligand binding sites. Ligands bind to either widen/narrow channels pores
How drugs target enzymes
Substrate analogues, false substrates and prodrugs
Substrate analogues Outline
Drugs bind to enzyme binding site preventing substrate from attaching
False Substrates Outline
Drugs that are close enough in shape to substrate that enzyme does convert it to product. The product is atypical (doesn’t preform the same actions)
Prodrug Outline
Prodrug (inactive) binds to enzyme receptor and leaves as an active drug species
Carrier Molecules Antagonist Interaction Outline
Antagonists bind either competitively or non-competively to transport protein. Molecules are unable to pass through
What is transported by transport proteins
Substances moving against their concentration gradient and hydrophilic molecules. Eg furosemide and hydrochoretizide block kidney to prevent Na+ kidney reabsorption
4 receptor classes
ligand-gated (fastest), g-protein coupled, enzyme linked receptors and nuclear receptors (slower)
Ligand gated ion channels Outline
Fastest (miliseconds). Especially ion gated
G-protein coupled Receptors Outline
Fast (seconds). Important for ANS. Metabatronic
Enzyme linked receptors Outline
Intermediately slow (hours) as it has multiple steps. Works by dimmerisation (bringing a receptor closer. undergoes phosphorylation in intracellular domain)
Nuclear Receptors
Slowest (hours to days) (as furthest distance travelled). Very potent effects signaling in cell
G-protein coupled receptors appearance Outline
Single polypeptide chain with 7 transmembrane loops (consisting of alpha helical regions). Extracellular regions = n-domains. intracellular regions = c-domains. Largest intracellular loop (c-domain) interacts with g-protein
3 G-protein coupled receptors families
A (rhodopsin), B (secretin/glucagon, peptide receptors) and C (glutamate/gaba receptors). Sequence homology within families (not between). Families show differences in n-terminal length and location of binding site from each other
3 subunits of g-protein receptors
Alpha (both anabolic and catalytic GTP), beta and gamma
G Alpha (s) Function
Stimulates adenylyl cyclase (increase cAMP)
G Alpha (i) Function
inhibits adenylyl cyclase (decrease cAMP)
G Alpha (q) Function
Activates phospholipase C. Increases secondary messages production: inositol phosphate and diacylglycerol
G Beta and Gama Function
Opens K+ channels, closes voltage gated Ca^2+ channels, activate GPCR kinases and activate mitogen-activated protein kinase cascade.
Norepinephrine and b-adrenergic receptor (G Alpha (s)) progression
Increase adenylyl cyclase = increased cAMP = increased protein kinase A = increase protein phosphorylation
Dopamine and Dopamine D2 receptors (G alpha (i)) progression
Decraesed adenylyl cyclase = decreased cAMP = decreased protein kinase A = decreased protein phosphorylation
Glutamate and mGluR ( G alpha (q)) progression
Phospholipase C production = diglyecerol and IP3 production = protein kinase C production = Ca^2+ release = increased protein phosphorylation
2 targets of g-proteins
adenylyl cyclase system and phospholipase C/IP3 system
Function of kinases and their control
Proteins are activated or inactivated by phosphorylation
Kinase Linked Receptors Appearance
Single chain, membrane spanning helical region. Large extracellular ligand binding domain. Intracellular domain varies in size and function
Kinase Linked Receptors Function
cell differentiation, dividion and immune response
3 classes of kinase receptors
Receptor tyrosine kinase, serinine/theronine kinase and cytosolic kinases (associate with cytokine reecptors with no intrinsic enzyme activity)
Steps of cytokine pathway
agonist binding, dimerisation, phosphorylation and gene transcription
Nuclear Receptors appearance
monomeric proteins, ligand activated transcription factors and located in cytosol or nucleus. Contains a DNA binding domain known as the hormone response element
