Ligands and Receptors Overview

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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?

Ligand-gated ion channel receptors (correct)

Intracellular receptors

Receptor tyrosine kinases

G-protein-coupled receptors

Which ions are primarily conducted by GABA receptors upon activation?

Na+ and K+

Ca2+ and Mg2+

Cl- (correct)

HCO3-

What structural characteristic defines GABAA receptors?

Pentameric structure with multiple subunits (correct)

Tetrameric structure with four distinct subunits

Dimeric structure with two identical subunits

Monomeric structure formed from single polypeptide

How do the properties of GABAA receptors change?

Depending on subunit combinations Signup and view all the answers

Which of the following is a common therapeutic target for benzodiazepines?

GABAA receptors Signup and view all the answers

What is the primary role of benzodiazepines such as diazepam and lorazepam?

Provide sedation and anxiolytic effects Signup and view all the answers

Which receptor family is associated with cascading effects mediated by G-proteins?

G-protein-coupled receptors Signup and view all the answers

Which G-protein is responsible for stimulating adenylate cyclase?

Gs Signup and view all the answers

What is a characteristic feature of muscarinic receptors?

Activated exclusively by acetylcholine with differing pharmacological properties Signup and view all the answers

Which muscarinic receptor subtype is associated with gastric secretion?

M1 Signup and view all the answers

Which of the following is a characteristic of receptor tyrosine kinases (RTKs)?

RTKs transfer phosphate groups from ATP to tyrosine residues. Signup and view all the answers

What is a potential therapeutic use of subtype-selective mAChR compounds?

To take advantage of differences in tissue distribution. Signup and view all the answers

Which type of receptor functions by altering protein activity through phosphorylation?

Receptor tyrosine kinases. Signup and view all the answers

What role does the Vascular Endothelial Growth Factor (VEGF) receptor play in the body?

It is essential for blood vessel formation. Signup and view all the answers

Which of the following receptors is NOT classified as a G-protein-coupled receptor (GPCR)?

Receptor tyrosine kinases. Signup and view all the answers

Which receptor family is primarily located in the cytosol and nucleus?

Intracellular receptors Signup and view all the answers

What type of receptors have an oligomeric assembly of subunits surrounding a pore?

Ligand-gated ion channel receptors Signup and view all the answers

What is the main effector of receptor tyrosine kinases?

Enzyme activation Signup and view all the answers

Which of the following receptor families couples via DNA to exert its effects?

Nuclear receptors Signup and view all the answers

What does the term 'non-selective' refer to when describing receptors?

Receptors that can bind multiple ligands without preference Signup and view all the answers

Which type of receptor has a structure that includes seven transmembrane domains?

G-protein-coupled receptors Signup and view all the answers

Which of these examples is a ligand-gated ion channel receptor?

Nicotinic receptor Signup and view all the answers

Which term describes the action of a receptor that directly affects ion channels?

Direct coupling Signup and view all the answers

Which adenosine receptor subtype is most likely mediating bronchial ring contraction in response to CPA?

A1 adenosine receptor Signup and view all the answers

What might be a primary reason for considering A1 receptor agonists in the treatment of refractory epilepsy?

They have shown anticonvulsant effects in mouse models. Signup and view all the answers

Which ligand would be expected to have the highest selectivity for A1 adenosine receptors given its Kd value?

Ligand A with Kd = 0.1 nM Signup and view all the answers

If a selective A2B adenosine receptor antagonist was introduced, what would be its expected impact on CPA-induced contraction?

No effect. Signup and view all the answers

In the context of bronchial rings, what is the expected outcome when using a non-selective adenosine agonist like CPA?

Increased tension. Signup and view all the answers

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.