Exam 1, ch. 2 review Flashcards
List receptor type based on molecular structure.
7TM receptors (GPCRs, 2/3rds of drugs bind to these), ligand-gated channels, ion channels.
Describe the cell signaling process.
Signaling molecule sends drug or endogenous ligand -> binds to receptor -> receptor sends signal transduction proteins/2nd messengers to the effector protein -> effector protein produces the change
Draw a phosphorylation cascade (generic).
Slide 8 of chapter 2 notes
Drug binds to receptor, conformation change, kinase is activated, kinase binds a phosphate group to another protein, activating it, and the 1st protein then binds phosphate to protein 2, activating it, and so forth. End result is activating effector protein.
Name 4 transmembrane signaling methods by which drug-receptor interactions exert their effects
Intracellular receptors (lipid soluble): uncharged
3 cell surface receptors:
-ion channels
-Catalytic (activates enzyme, e.g. phosphorylation cascade)
-GPCRs
Define the structure of GPCRs and their components
Receptor is seven trans-membrane helices, G-proteins are attached inside the receptor. G-proteins have alpha beta and gamma proteins attached to them. There are effector proteins the g-protein will bind to, which produce second messenger cells that protein kinase will bind to, to produce an effect.
Define the structure of RTKs and their components
Receptor Tyrosine Kinsase
On cell surface, Receptor itself is the kinase and itself activates effector protein. Drug binds to 2 receptors, they dimerize and become 1 receptor. Then phosphate (from ATP, need 6 ATP molecules) groups bind to Tyrosine inside the cell, activating the receptor to interact with effector proteins to produce downstream effects.
Elucidate the mechanism of GPCR signaling
GPCR has a drug/ligand bind to it, activates g-protein, which detaches itself from GDP and binds to GTP, G-protein alpha then binds to the effector protein, which activates second messenger cascade, producing effect. G-protein then dumps GTP and binds back to GDP at receptor site and now deactivated.
Describe the role of second messengers, and list the most common as described in
lecture
cAMP, calcium, DAG, IP3.
- Second messengers are produced by the first effector protein, turning ATP into a second messenger such as cAMP. Second messenger then binds to protein kinase A (attaches phosphate group), and produces cellular responses
Define desensitization and describe the molecular components of desensitization in the
GPCR.
Slide 32 for drawn out visual view.
Desensitization is when the drugs effect on the body is strong at first and then decreases as time passes.
-After the drug binds to receptor and downstream effects start, after a while b-arrestin proteins will bind to OH groups on effector protein, resulting in blocking signaling cascade. A clatherin coated pit is formed around the receptor, further making it ineffective.
2 possibilities from here: 1 the drug can escape and receptor gets recycled, returning to cell surface. Or 2, a lysosome binds to clatherin pit and destroys receptor.
Similarities for ligand gated and voltage gated ion channels.
Water soluble, ion specific channels that move across a gradient, determined by concentration of ions.
Voltage gated channels
Found in excitable cells – neurons, muscle, endocrine cells
Closed at resting membrane potential (normal charge for that membrane) e.g. Ca++, K+, Na+ channels.
Speed of certain ion channels
Calcium is very slow, Sodium is fast.
Ligand gated ion channels
Ionotropic - more common, has a ligand bonding site and channel on same protein. e.g. ACh binds and it opens the channel for sodium to flow in the skeletal muscle cells
Metabotropic has the ligand bind which activates GPCR, and second messenger activity opens the channel.
List the types of ligands that bind to receptors inside the cell
Gasses and lipid soluble agents
