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Questions and Answers
What type of receptor is primarily activated by endogenous ligands to allow ion passage through the cell membrane?
Which ions are primarily conducted by GABA receptors upon activation?
What structural characteristic defines GABAA receptors?
How do the properties of GABAA receptors change?
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Which of the following is a common therapeutic target for benzodiazepines?
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What is the primary role of benzodiazepines such as diazepam and lorazepam?
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Which receptor family is associated with cascading effects mediated by G-proteins?
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Which G-protein is responsible for stimulating adenylate cyclase?
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What is a characteristic feature of muscarinic receptors?
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Which muscarinic receptor subtype is associated with gastric secretion?
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Which of the following is a characteristic of receptor tyrosine kinases (RTKs)?
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What is a potential therapeutic use of subtype-selective mAChR compounds?
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Which type of receptor functions by altering protein activity through phosphorylation?
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What role does the Vascular Endothelial Growth Factor (VEGF) receptor play in the body?
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Which of the following receptors is NOT classified as a G-protein-coupled receptor (GPCR)?
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Which receptor family is primarily located in the cytosol and nucleus?
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What type of receptors have an oligomeric assembly of subunits surrounding a pore?
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What is the main effector of receptor tyrosine kinases?
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Which of the following receptor families couples via DNA to exert its effects?
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What does the term 'non-selective' refer to when describing receptors?
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Which type of receptor has a structure that includes seven transmembrane domains?
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Which of these examples is a ligand-gated ion channel receptor?
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Which term describes the action of a receptor that directly affects ion channels?
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Which adenosine receptor subtype is most likely mediating bronchial ring contraction in response to CPA?
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What might be a primary reason for considering A1 receptor agonists in the treatment of refractory epilepsy?
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Which ligand would be expected to have the highest selectivity for A1 adenosine receptors given its Kd value?
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If a selective A2B adenosine receptor antagonist was introduced, what would be its expected impact on CPA-induced contraction?
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In the context of bronchial rings, what is the expected outcome when using a non-selective adenosine agonist like CPA?
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Study Notes
Ligands & Receptors
- Ligands are molecules that bind to receptors.
- Ligands can be endogenous (e.g. neurotransmitters, hormones, inflammatory mediators) or exogenous (e.g. drugs).
- Ligand binding to a receptor alters the receptor's conformation, triggering a cellular response.
Receptor Families
- Four main receptor families:
- Ligand-gated ion channel receptors (ionotropic receptors)
- G-protein-coupled receptors (GPCRs)
- Receptor tyrosine kinases (RTKs)
- Intracellular receptors
Ligand-gated Ion Channel Receptors
- Activated by binding of endogenous ligands.
- Allow ion passage through the impermeable cell membrane.
- Ion conductivity is highly selective (e.g. GABA receptors for Cl- ions, Glutamate receptors for Na+ and K+ ions).
- Multi-protein subunit assemblies mediate fast signaling at synapses (fraction of a millisecond).
Example: GABAA Receptors
- GABA is the main inhibitory neurotransmitter.
- GABAA receptors are ligand-gated ion channel receptors.
- Pentameric structure formed from two α, two β, and one γ subunit, with multiple subunit isoforms.
- Receptor properties vary depending on subunit combination.
- GABA binding site formed by peptide loops between an α and β subunit.
- Therapeutic use:
- Main drug target for benzodiazepines (e.g. diazepam, lorazepam, clobazam).
- Benzodiazepine binding site is formed between the α and γ subunit.
- Applications: sedation, anxiolytic, epilepsy treatment.
G-protein-coupled Receptors (GPCRs)
- Monomeric proteins with 7 transmembrane domains.
- Coupled to G-proteins:
- Gi: inhibits adenylate cyclase
- Gs: stimulates adenylate cyclase
- Gq: activates phospholipase C
- Mediates activation of downstream signaling cascades leading to a cellular response.
Example: Muscarinic Receptors
- Five muscarinic receptor subtypes: M1, M2, M3, M4, and M5.
- All activated by acetylcholine (non-selective).
- Differences in primary structure, tissue distribution, pharmacological properties, and signal transduction activity.
Other Drugs Acting through GPCRs
- β-adrenoceptors: isoprenaline
- Adenosine receptors: caffeine, theophylline
- Dopamine receptors: L-dopa, haloperidol
- Opioid receptors: morphine, codeine
- Serotonin receptors: buspirone, ondansetron
- Cannabinoid receptors: cannabis, rimonabant, Sativex
Receptor Tyrosine Kinases (RTKs)
- Extracellular ligand binding domain and intracellular kinase enzyme domain.
- Transfer phosphate groups from ATP to tyrosine residues on target proteins (phosphorylation).
- Phosphorylation controls protein function by:
- Altering enzyme activity (on/off state)
- Changing subcellular location
- Modifying interactions with other proteins (adaptor proteins, kinases, phosphatases, lipases)
Example: Vascular Endothelial Growth Factor Receptors (VEGF Receptors)
- Essential for angiogenesis (blood vessel formation) during development, pregnancy, and wound healing.
- Associated with pathophysiological conditions like heart disease and limb ischemia.
Nuclear/Steroid Hormone Receptors
- Located in the cytosol and nucleus.
- Hormone (ligand) binds to the receptor, forming a dimer that translocates to the nucleus.
- Acts as a transcription factor to stimulate target gene expression.
Receptor Summary
- Ligand-gated ion channels: direct coupling, rapid signaling, ion channel as effector (e.g. nicotinic, GABAa).
- GPCRs: G-protein coupling, mediated by downstream signaling cascade, channel or enzyme as effector (e.g. dopamine, cannabinoid, adenosine, muscarinic).
- Kinase-linked receptors: direct coupling, kinase enzyme as effector (e.g. insulin, growth factors, cytokines).
- Nuclear receptors: hormone-receptor dimer translocates to nucleus, gene transcription as effector (e.g. steroid, thyroid hormone).
Adenosine Receptor Subtypes
- Adenosine receptors can be A1 or A2B.
- Non-selective adenosine agonist CPA can induce bronchial ring contraction.
- Selective A1 antagonist 8-CPT blocks contraction induced by CPA, suggesting A1 receptor involvement.
- Selective A2B antagonist PSB-601 does not prevent CPA-induced contraction, indicating A2B is not the primary mediator.
- A1 receptor agonists have anticonvulsant effects in mouse models of epilepsy.
- Testing an A1 receptor agonist in a clinical trial for refractory epilepsy might be worthwhile, but further investigation is needed.
Ligand Affinity
- Kd value reflects ligand affinity for a receptor.
- Lower Kd value indicates higher affinity.
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Description
Explore the fascinating world of ligands and receptors in cellular communication. This quiz covers the types of ligands, receptor families, and the function of ligand-gated ion channels, focusing on examples like GABAA receptors. Test your understanding of these essential biological concepts and their implications in pharmacology and neuroscience.
