What are the four main types of receptors that drugs can act on?
1) Ligand-gated ion channels, 2) G-protein coupled receptors (GPCRs), 3) Kinase-linked receptors, and 4) Nuclear receptors.
What are ligand-gated ion channels?
Receptors that open to allow ions to flow across the membrane when activated by a ligand.
What is the natural ligand for the nicotinic acetylcholine receptor?
Acetylcholine.
Where are nicotinic acetylcholine receptors found?
On muscle cells (regulating contraction) and on neurons (regulating firing).
Describe the structure of the nicotinic acetylcholine receptor.
It has five protein subunits, each with four transmembrane domains (M1–M4).
Which domain forms the channel gate in nicotinic receptors?
The M2 domain, which faces the pore and contains hydrophobic amino acids like valine and leucine.
What type of ions flow through nicotinic acetylcholine receptors?
Sodium (Na+) ions.
Where is the acetylcholine binding site located?
At the interface between adjacent subunits of the receptor.
How does acetylcholine binding open the ion channel?
It causes conformational changes that rotate the M2 helices away from the pore, opening the channel.
List other ligand-gated ion channels with similar structure.
GABAA receptor, 5-HT3 (serotonin) receptor, and glycine receptor.
List some antagonists of the nicotinic acetylcholine receptor.
Tubocurarine (causes paralysis), atracurium (clinical use), and α-bungarotoxin (cobra venom).
What are examples of GABAA receptor antagonists and their effects?
Picrotoxin (from fishberry) blocks chloride flow and can cause convulsions.
List agonists or modulators of ligand-gated ion channels.
Nicotine (activates nicotinic ACh receptors), benzodiazepines (enhance GABA action), and muscimol (GABA agonist).
What are GPCRs?
Receptors with seven transmembrane domains that activate intracellular G-proteins upon ligand binding.
What are examples of GPCRs?
Muscarinic acetylcholine receptors, adrenoceptors, dopamine receptors, and opiate receptors.
Describe the structure of GPCRs.
A single polypeptide chain with an extracellular N-terminus, intracellular C-terminus, and 7 transmembrane helices (M1–M7).
What are the three subunits of G-proteins?
Alpha (α), beta (β), and gamma (γ).
What happens when a ligand binds to a GPCR?
A conformational change allows the receptor to activate G-proteins, replacing GDP with GTP on the α-subunit.
What happens after GTP binds to the α-subunit?
The α-subunit dissociates from the βγ complex and interacts with target proteins like enzymes or ion channels.
How is GPCR signaling terminated?
The α-subunit’s GTPase activity hydrolyzes GTP to GDP, allowing reassociation with the βγ complex.
What are the two types of GPCR signaling pathways?
Stimulatory (Gs) and inhibitory (Gi).
Give an example of opposing GPCR effects in the heart.
Muscarinic receptors inhibit and β-adrenoceptors stimulate heart contraction.
What enzyme do Gs and Gi proteins regulate?
Adenylate cyclase (AC).
What does adenylate cyclase produce?
Cyclic AMP (cAMP) from ATP.
