Pharmacology:
Lecture 2:
Receptors:
-Ion channels:
-Multi-subunit ion channels
-Location: cell surface transmembrane
-Bindingion influxeffect on cell excitability
-Examples of ligands: acetylcholine, GABA, glutamate, glycine
Allosteric modulator: when a drug binds to a different part of the receptor.
-Protein kinases:
-Location: cell surface
-Ligands: growth factors, peptide hormones
-Proteins become activated after binding open or close
-Transcription factors:
-Location: cytoplasm
-Ligands: steroid hormones, thyroid hormone, vitamin D
-Activation/suppression DNA transcription
-G-protein coupled receptors:
-Location: cell surface, 7 TM
-Ligands: acetylcholine, a- B-adrenergic eicosanoids
-GTPGDP
-One of most important drug targets
Step 1: ligand binds to receptor, Bg get split off and move to target 2
Step 2: a splits off receptor and moves to target 1. a receives GTP before
move.
Step 3: GTP in a splits off P GDP. Target 1 and 2 activated
Step 4: ka and Bg bind back to receptor. What happens next depends on
target effector protein.
CAMP system:
-Second messenger
-Activated G-protein activates adenylyl cyclase ATP-cAMP activates protein kinase A
, -G-protein that activates cAMP formation: stimulatory G-protein
Regulating GPCR signaling-off signal
-GTP activated a-subunit has intrinsic GTP-ase activity
-Phosphodiesterase hydrolyses cAMP AMP
-Without these mechanisms, no turning off receptors
Receptor desensitization:
-Some receptors are phosphorylated via specific receptor kinases
-The phosphorylated receptor may then bind to a protein b-arrestin that promotes removal
of the receptor.
Inhibitory G-proteins: inhibits adenylate cyclase
-Cannabinoid receptors:
-Important endogenous regulation
-2 G-protein coupled receptors so far
-Many endogenous end exogenous cannabinoids
-Specific transporters
-Appetite stimulation
-Hallucinogenic euphoric
-Anti-inflammatory
We have our own endocannabinoid system in fatty acids increased in obesity
Receptor models:
Agonist: locked in active state
Antagonist: keeps receptor neutral, prevents agonist from binding
Competitive antagonist: binds at same site as agonist
Non-competitive antagonist: binds on different site
Reversible/irreversible
Inverse agonism : actively pushes receptor in active mode
Lecture 2:
Receptors:
-Ion channels:
-Multi-subunit ion channels
-Location: cell surface transmembrane
-Bindingion influxeffect on cell excitability
-Examples of ligands: acetylcholine, GABA, glutamate, glycine
Allosteric modulator: when a drug binds to a different part of the receptor.
-Protein kinases:
-Location: cell surface
-Ligands: growth factors, peptide hormones
-Proteins become activated after binding open or close
-Transcription factors:
-Location: cytoplasm
-Ligands: steroid hormones, thyroid hormone, vitamin D
-Activation/suppression DNA transcription
-G-protein coupled receptors:
-Location: cell surface, 7 TM
-Ligands: acetylcholine, a- B-adrenergic eicosanoids
-GTPGDP
-One of most important drug targets
Step 1: ligand binds to receptor, Bg get split off and move to target 2
Step 2: a splits off receptor and moves to target 1. a receives GTP before
move.
Step 3: GTP in a splits off P GDP. Target 1 and 2 activated
Step 4: ka and Bg bind back to receptor. What happens next depends on
target effector protein.
CAMP system:
-Second messenger
-Activated G-protein activates adenylyl cyclase ATP-cAMP activates protein kinase A
, -G-protein that activates cAMP formation: stimulatory G-protein
Regulating GPCR signaling-off signal
-GTP activated a-subunit has intrinsic GTP-ase activity
-Phosphodiesterase hydrolyses cAMP AMP
-Without these mechanisms, no turning off receptors
Receptor desensitization:
-Some receptors are phosphorylated via specific receptor kinases
-The phosphorylated receptor may then bind to a protein b-arrestin that promotes removal
of the receptor.
Inhibitory G-proteins: inhibits adenylate cyclase
-Cannabinoid receptors:
-Important endogenous regulation
-2 G-protein coupled receptors so far
-Many endogenous end exogenous cannabinoids
-Specific transporters
-Appetite stimulation
-Hallucinogenic euphoric
-Anti-inflammatory
We have our own endocannabinoid system in fatty acids increased in obesity
Receptor models:
Agonist: locked in active state
Antagonist: keeps receptor neutral, prevents agonist from binding
Competitive antagonist: binds at same site as agonist
Non-competitive antagonist: binds on different site
Reversible/irreversible
Inverse agonism : actively pushes receptor in active mode
