12-RECEPTORS – Dr. Groseclose Flashcards
What are the major types of receptors?
Acetylcholine ATP (purine) gamma-aminobutyrate (GABA) glutamate serotonin (5HT)
For Acetylcholine (type of nicotinic cholinergic) receptors, how many and what type of subunits make up acetylcholine? Where is it located? Name an example of an acetylcholine receptor
heterodimer (5 subunits - 2 alpha, one beta, 1 gamma, 1 delta)
Located spanning the cell membrane
ex. Na+/K+ channel
For G-Protein coupled receptors (GPCRs), how many and what type of subunits make up GPCR? Where is it located?
What does it bind to and what is the response time?
Has one or two subunits (one subunit spans the membrane with 7 domains)
Located inside the membrane
Receptor engages proteins that bind GUANINE (hence G-proteins). G-protein has 3 subunits.
Interact with effector molecule via G-protein
Describe the structure of PARs. What superfamily do PARs belong to? What activates each of the four PARs? Which PARs? Which two are found on human platelets?
β receptor has 7 span shape. It is activated by thrombin/trypsin.
Thrombin = Par 1,3,4.
Trypsin = Par 2.
PAR1 and PAR4 are found on human platelets.
Describe the Phototransduction pathway
Light activates Rhodopsin to undergo a conformational change that allows it to bind to an inner membrane G-protein. When the G-protein binds, the ALPHA subunit undergoes a conformational change and is released as alpha-GTP. Alpha-GTP binds and activates cyclic-GMP phosphodiesterase. Which can now convert CGMP to GMP. When consumed, alpha-GTP is converted to alpha-GDP.
What physical characteristics distinguish the groups of receptors from each other? (ie. Location within the cell, subunit structure, distinctive 2o structure such as 7-span)
Intracellular receptors are located within the nucleus of the cells. The other three types are located in the cell membrane.
- Ligand-gated ion channel has five similar subunits that open an ion passageway.
- Insulin-like receptors are able to phsophorylate themselves and attach phosphates to tyrosine residues.
- G-protein coupled receptors include a special PAR receptor that has a 7-span shape
Discuss the various ways in which activated receptors accomplish their cellular effects. (ie. Increasing or decreasing cyclic nucleotides, changing ionic permeability, altering transcription)
Ligand-gated ion channels open up ion passageways and therefore the receptors work based on their changed ionic permeability.
G-protein coupled receptors are activated after being bound by a hormone where they then affect cAMP and cGMP and cause an effect on an effector molecule (ie. Other kinases, β-adrenergic receptors).
PARs (protease activated receptors) are G-protein linked receptors that are activated by the proteolytic removal of a portion of the N-terminus of the 7 span shaped receptor by either thrombin or trypsin.
Insulin-like receptors are those that work by attaching phosphates to tyrosine residues (phosphorylation)
Intracellular receptors work after the ligand diffuses into the cell membrane and binds to the receptor. The ligand-receptor complex acts in the nucleus by altering transcription.
Discuss the different ways in which receptors can be characterized.
- Location: Surface of cell/Interior of cell {span the membrane?}
- Type of Interaction: Ligand (agonist vs. antagonist)
- # of subunits
- Mechanism of Action: Ionotropic vs. Metabotropic
- Response time
What is a ligand?
the substance that binds to a receptor
What is an agonist?
stimulating the receptor physiologically by acting as “native” ligand
What is an antagonist?
prevents activity, or inhibits the receptor’s usual response
What is a receptor?
cellular proteins located on the cell surface or cell interior that interact with molecules like hormones, toxins, cytokines, drugs, and neurotransmitters
What characteristic of the protease activated receptors (PARs) is unique?
PARs (G-protein linked receptors) are unique in that their mechanism of Activation: they are activated by the proteolytic removal of a portion of the N-terminus of the receptor itself. Therefore the new N-terminus generated IS the ligand.
Discuss the gross structure of G-proteins.
G-proteins are comprised of 3 subunits (alpha-the largest, beta, and gamma)
EC_50 vs K_D: Which of these values describes binding of receptor and ligand? Which of these describes effectiveness in eliciting a cell response?
K_D = ligand concentration for half maximal occupancy of receptors
EC_50 = ligand concentration for half-maximal cellular response
