Receptors Ch 5 & 8 Flashcards
Structure of receptors
Globular proteins, mostly in the cell membrane. Contains a hydrophobic hollow or cleft on its surface that functions as binding site.
Function of receptors
Receive messages from chemical messengers and transmit them into the cell
2 Types of Chemical Messengers
Released from?
Lifespan?
Neurotransmitters: released from nerve endings that cross a synapse to bind to receptor. Short lived. Between individual cells.
Hormones: released from gland and bind to target cells throughout the body.
Chemical Messenger definition and 6 specific ex.
Switch on receptors without undergoing a chemical reaction. Ex. acetylcholine, adrenaline, dopamine, serotonin, aminobutyric acid, glutamic acid.
Signal Transduction
Domino effect resulting from induced fit when messenger binds via weak forces leading to chemical signal inside cell.
Binding interaction strength
Strong enough to hold messenger for signal transduction to take place.
Weak enough to allow messenger to depart.
Antagonist
Bind more strongly than messenger to binding site, but does not elicit response
Agonist
Binds reversibly to binding site and elicits response. Similar in structure to natural messenger.
Ion channel structure
Five glycoprotein subunits tranversing cell membrane with receptor integrated into alpha helix subunits making hydrophillic channel in center. Has open and closed conformation.
Ion channel function
Allow specific ions to to cross cell membrane down concentration gradient, depolarizes nerve membranes
Inhibitory vs. Excitatory ion channels with examples
Inhibitory: Chloride ions (ex. GABA)
Exhibitory: Potassium, Sodium, Calcium ions (ex. nicotinic)
G-protein coupled receptor with example
7 pass transmembrane helix with ligand binding site on the extracellular side and G-protien binding site on intracellular side (ex.Rhodopsin)
G-protein coupled receptor function
Binding of messenger leads to induce fit that causes G protein to bind and bind GTP (enzyme function), splitting into alpha and beta-gamma subunits.
G-protein function with 2 examples
Alpha s subunit activates membrane bound enzyme (ex. adenylate cyclase, phospholipase C). Inactivated when GTP is hydrolyzed to GDP.
Adenylate cyclase
Activated by alpha s subunit, converts ATP to cyclic AMP.
Competitive reversible antagonist
Effect of increasing concentration of messenger?
Binds noncovalently but different induced fit occurs so receptor is not activated. Increasing concentration reverses antagonism.
Non competitive irreversible antagonists
Effect of increasing concentration of messenger?
Binds covalently but different inducted fit occurs so receptor is not activated. Increasing concentration has no effect.
Noncompetitive reversible allosteric antagonist
Effect of increasing concentration of messenger?
Binds noncovalently to allosteric site. Increasing concentration has no effect.
Antagonists by proximity effect
Binds reversibly to neighboring binding site and overlaps with messenger binding site (Noncompetitive).
Partial agonist
Binds to receptor but causes conformational change that is not ideal or is able to bind to receptor in two ways, acting as an agonist in one method and as an antagonistic in the other.
Inverse agonist
Binds to receptor and shuts down constitutive activity.
Super agonist
Binds to receptor and elicits more than full biological response.
Desensitization/Sensitization
Desensitization: endocytosis of receptors or reduced receptor biosynthesis, phosphorylation of receptor.
Sensitization: increased receptor synthesis.
Dependence
need to take drug to have normal response that can occur with both agonists and antagonists due to increase receptor synthesis (sensitization).
Alpha s subunit
Stimulates adenylate cyclase
Alpha i subunit
Inhibits adenylate cyclase and may activate potassium channel
Alpha o subunit
Inhibit neuronal calcium ion channels
Alpha q subunit
Activates phospholipase C
Tolerance
Higher dosage of drug required to produce the same effect by increasing the number of receptors.
Phospholipase C
Cleaves phosphatidylinositol diphosphate (PIP2) into diacylglycerol (DG) and inositol triphosphate (IP3).
Diacylglycerol
Hydrophobic secondary messenger activate protein kinase C (PKC).
Inositol triphosphate
Hydrophilic secondary messenger that opens calcium channels in the endoplasmic reticulum to activate calcium dependent protein kinases and calmodulin.
