How Drugs Act: Molecular and Cellular Aspects Flashcards
What is the job of the receptors?
▪ Protein molecule which function to recognize and respond to endogenous chemical signals
- recognize/bind specific endogenous ligands
- may also recognize/bind xenobiotics
What are receptors classified by?
ligand
What are the four superfamiles of receptors?
- Ligand-Gated Ion Channels
- G-Protein Coupled Receptors
- Kinase-Linked & Related Receptors
- Nuclear Receptors
What is the general name of the ligand-gated ion channels?
— “ionotropic” receptors
What is the general name of the G-protein coupled receptors?
— “metabotropic” receptors
— “7 trans-membrane spanning domain” receptors
— “heptahelical” receptors
— “serpentine” receptors
What is the general name of the kinase-linked and related receptors?
— large and heterogeneous group
— single trans-membrane spanning domain
What is the general name of the nuclear receptors?
“steroid superfamily”
What is the main example of a ligand-gated ion channel?
nicotinic acetylcholine receptor
What is the main example of a g-protein coupled receptor?
opioid receptors
What is the main example of a kinase-linked and related receptor?
insulin receptors
What is the main example of a nuclear receptor?
androgen receptors
Where are ligand-gated ion channels located?
plasma membrane
Ligand-Gated Ion Channels Composed of ____ of these subunits
4-5
Where are G-protein coupled receptors located?
plasma membrane
What is unique about kinase-linked and related receptors?
generally one transmembrane spanning domain
Why are there different receptor subtypes?
- different genes, different phenotypes
— different genes may encode for different subtypes - same gene, different phenotypes
— variation may arise from alternative mRNA splicing
— single nucleotide polymorphisms
What are the features of receptor subtypes?
- receptors in given family generally occur in several molecular varieties or “subtypes”
— similar architecture
— significant differences in amino acid sequence
— often different pharmacologic properties
— nicotinic acetylcholine receptor subtypes occur in different brain regions and these differ from subtype in muscle
What are examples of ligand-gated ion channels?
— nicotinic acetylcholine receptor (nAChR)
— gamma-aminobutyric acid type A receptor (GABAA)
— glutamate receptors
What are ligand-gate ion channels?
- share structural features with voltage-gated ion channels
- “ionotropic” receptors
What is important to know about nicotinic acetylcholine receptor (nAChR)?
— pentamer: four different polypeptide subunits
— transient opening of central aqueous channel
— Na+ flow from outside to inside cell
— cell depolarizes
— all occurs in milliseconds
What does the formation of an ion channel through the nicotinic acetylcholine receptor (nAChR) allow for?
movement of Na+ from outside cell to inside
What is the largest superfamily of receptors?
G-protein coupled receptors
What are examples of G-protein coupled receptors?
— muscarinic acetylcholine receptor (mAChR)
— opioid receptors (u, k, s)
— gamma-aminobutyric acid type B receptor (GABAB)
— serotonergic receptors
— adrenergic receptors ( and types)
— angiotensin II receptors (1, 2, 3, 4 types)
— endothelin receptors (A, B, C types)
— histamine receptors (1, 2, 3 types)
— photon receptors (retinal rod and cone)
How do G-protein coupled receptors work (specifically opioid receptors)?
- agonist binds to region inside receptor surrounded by
7 TM domains - conformational change in cytoplasmic side
- G-Protein affinity for nucleotide GDP is reduced
- GTP binds
- GTP-bound G-Protein dissociates from the receptor
- GTP-bound G-Protein engages downstream mediators (a.k.a. “effectors”)