Receptor Theory and Signaling Mechanisms Flashcards
Pharmacodynamics
What the drug does to the body
Receptor interactions
Determine
- Quantitative relationship between Dose and Effect
- Selectivity of Drug action
Agonist
Acts at a receptor and produces a response.
Has Affinity for the Receptor and
Has Intrinsic Activity at that Receptor.
Antagonist
Decreases the Effect of the Agonist
Competitive Antagonist
Has Affinity for the Same Receptor as the Agonist.
Binds to the Receptor, Blocking the Agonist from Binding to the Receptor.
Lacks Intrinsic Activity.
Inverse Agonist
Some Receptors have Constitutive Activity. They exist in Equilibrium between inactive and active forms.
- -In the Active form, they cause effects without an agonist being necessary.
- -Thus, they have basal activity.
–Agonists bind to the receptor and push the equilibrium (conformation) to the Active form.
- -Inverse Agonists bind to and stabilize the Inactive Conformation, pushing the equilibrium away from the active form
- -Thus, Decreasing Activity.
Inverse Agonists have Affinity and Intrinsic Activity!
Binding of Drugs to Receptors
Usually the initial forces of attraction are Ionic.
Van der Waals forces and H bonds are important in binding the drug to the receptor.
Covalent bonds are not common in drug receptor interactions; they are irreversible.
Receptor Mediated Signaling Pathways
Transmembrane
Most commonly, receptors are on outside of cell membrane.
Second messengers in cytoplasm.
Almost all second messenger signaling involves Phosphorylation/ Dephosphorylation reactions, which amplify and flexibly regulate the signaling.
Lipid Soluble Agents
Lipid soluble drug crosses cell membrane to enter cell.
Interacts with intracellular receptors (often nuclear receptors).
Activates enzymes or Regulates gene expression.
Ultimate effect is in the Nucleus.
Steroid hormones are good example.
Regulation of Gene Expression
Lag period
Effects can persist long after the agonist is no longer detectable.
Ligand-Gated Ion Channels
Drug acts from Outside cell.
Binds to Ion channel.
Regulates opening of the ion channel.
Results in Changes in intracellular ion concentrations and produces changes in cellular functions.
-Quick action/response.
Ligand Regulated Enzymes
Drug acts Outside cell by Binding to Extracellular Domain of Transmembrane Receptor.
This Activates Enzymatic activity in the Cytoplasmic domain
Receptor Tyrosine Kinase
Drug acts Outside cell by binding to Extracellular Domain of Transmembrane Receptor.
Intracellular Protein Kinase is activated.
Phosphorylation of intracellular proteins occurs right at the intracellular domain of the receptor.
Receptors Coupled to G Proteins
Receptor crosses membrane 7 times (Serpentine)
Cell surface receptor that is coupled to G protein.
Effector Enzyme is activated.
Second Messenger is generated.
Examples:
- -Adenylate Cyclase (enzyme) gives cAMP (2nd messenger), cGMP;
- -Phospholipase C (PLC) (enzyme) gives DAG and IP3 (2nd messengers)
