L 3 Flashcards
- What are the four main types of receptors that drugs can act on?
Answer: The four main types of receptors that drugs can act on are:
Ligand-gated ion channels
G-protein coupled receptors (GPCRs)
Enzyme-linked receptors
Intracellular (nuclear) receptors
- How do ligand-gated ion channels function?
Answer: Ligand-gated ion channels function by allowing ions to flow across membranes when activated by a ligand, such as a neurotransmitter. The ligand binds to the channel, causing a conformational change that opens the channel and permits ion flow, which may lead to depolarization and the generation of an action potential.
- Describe the structure of the nicotinic acetylcholine receptor and its role in ion conduction.
Answer: The nicotinic acetylcholine receptor is a ligand-gated ion channel made up of five protein subunits arranged in a ring, each passing through the membrane four times (M1-M4 domains). The second transmembrane domain (M2) lines the pore of the channel and forms the channel gate. When acetylcholine binds to the receptor, it induces a conformational change that opens the pore, allowing Na+ ions to flow into the cell, leading to depolarization.
- What are some examples of drugs and toxins that affect ligand-gated ion channels?
Answer: Examples of drugs and toxins that affect ligand-gated ion channels include:
Nicotinic acetylcholine receptor antagonists: Tubocurarine (causes paralysis, blocks acetylcholine binding), α-bungarotoxin (from cobra venom, blocks receptor, causing paralysis).
Nicotinic acetylcholine receptor agonist: Nicotine (activates the receptor).
GABAA receptor modulator: Benzodiazepines (enhance GABA action, causing relaxation).
GABAA receptor antagonist: Picrotoxin (blocks ion flow through the GABAA receptor channel).
- How do G-protein coupled receptors (GPCRs) function and what is their structure?
Answer: GPCRs consist of a single polypeptide chain with an extracellular N-terminus, intracellular C-terminus, and seven transmembrane domains (M1-M7). When a ligand binds to the extracellular domain, the receptor undergoes a conformational change, allowing it to interact with G-proteins (composed of α, β, and γ subunits). This interaction causes GDP to be replaced by GTP on the α-subunit, leading to the dissociation of the G-protein. The α-subunit can then activate or inhibit downstream targets such as enzymes or ion channels. The process ends when the GTP is hydrolyzed to GDP, and the G-protein reassembles.
- What is the role of adenylate cyclase (AC) in GPCR signaling, and how is it regulated?
Answer: Adenylate cyclase (AC) is an enzyme that converts ATP to cyclic AMP (cAMP), a second messenger that regulates various cellular functions. GPCRs can either stimulate (via Gs proteins) or inhibit (via Gi proteins) AC activity. The level of cAMP within the cell is controlled by these interactions, which in turn regulates the activity of protein kinases, ion channels, and other proteins. For example, cAMP activates protein kinase A (PKA), which can phosphorylate proteins involved in processes like muscle contraction and metabolic regulation.
- What are some physiological functions of β-adrenoceptors, and how are they targeted by drugs?
Answer: β-adrenoceptors are involved in regulating heart contraction and glycogen metabolism in the liver. Agonists such as adrenaline (epinephrine) activate these receptors, increasing heart rate and promoting glycogen breakdown. Drugs targeting β-adrenoceptors, such as propranolol (a β-blocker), act as antagonists, reducing heart rate and blood pressure, making them useful in treating conditions like hypertension and arrhythmias.
- What are some other common targets for G-proteins besides adenylate cyclase?
Answer: In addition to adenylate cyclase, G-proteins can target:
Phospholipase C (PLC): Produces two intracellular messengers, IP3 and DAG. IP3 increases cytosolic Ca2+ by releasing it from intracellular stores, leading to processes like muscle contraction and enzyme activation. DAG activates protein kinase C, which phosphorylates a variety of proteins, controlling many cellular functions.
Ion channels: G-proteins can regulate calcium, potassium, and sodium channels, affecting processes such as neurotransmitter release and muscle contraction.
- How do muscarinic acetylcholine receptors differ from nicotinic acetylcholine receptors, and what effect do they have on cardiac cells?
Answer: Muscarinic acetylcholine receptors are G-protein coupled receptors, unlike the nicotinic acetylcholine receptors, which are ligand-gated ion channels. In cardiac cells, muscarinic acetylcholine receptors are inhibitory, decreasing heart rate by activating Gi proteins, which inhibit adenylate cyclase and reduce cAMP levels. This contrasts with β-adrenoceptors, which stimulate heart rate by increasing cAMP production through Gs proteins.
- What are the main intracellular messengers produced by phospholipase C, and what roles do they play in cellular signaling?
Answer: Phospholipase C produces two intracellular messengers:
Inositol trisphosphate (IP3): Increases cytosolic calcium levels by releasing calcium from intracellular stores, leading to processes such as muscle contraction, secretion, and enzyme activation.
Diacylglycerol (DAG): Activates protein kinase C, which phosphorylates various proteins involved in cellular functions like metabolism and cell division.
