G-protein coupled receptors MCQs With Answer

G-protein coupled receptors MCQs With Answer

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G-protein coupled receptors (GPCRs) are a vast family of seven-transmembrane (7TM) proteins central to pharmacology and cellular signal transduction. For B.Pharm students, a firm grasp of GPCR structure, ligand binding, G-protein coupling (Gs, Gi, Gq), second messengers (cAMP, IP3/DAG, Ca2+), receptor desensitization, arrestin biology, biased agonism and therapeutic targeting is essential for rational drug design and clinical practice. Key concepts include orthosteric versus allosteric modulation, constitutive activity, receptor internalization, assay techniques (radioligand binding, functional response assays) and representative drug classes (β-adrenergic, muscarinic, opioid, histamine). Mastery of these topics aids in understanding drug action, adverse effects and novel therapies. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which structural feature characterizes G-protein coupled receptors (GPCRs)?

  • Single transmembrane helix
  • Seven transmembrane alpha helices
  • Single-pass beta-sheet domain
  • Extracellular ligand-gated pore

Correct Answer: Seven transmembrane alpha helices

Q2. Activation of which G protein class typically increases intracellular cAMP via stimulation of adenylate cyclase?

  • Gi
  • Gq
  • Gs
  • G12/13

Correct Answer: Gs

Q3. Which G-protein subtype inhibits adenylate cyclase and reduces cAMP levels?

  • Gs
  • Gi
  • Gq
  • Gs/Gq heterodimer

Correct Answer: Gi

Q4. Activation of Gq-coupled receptors primarily triggers which downstream enzyme and second messengers?

  • Adenylyl cyclase; cAMP
  • Phospholipase Cβ; IP3 and DAG
  • Guanylyl cyclase; cGMP
  • Phospholipase A2; arachidonic acid

Correct Answer: Phospholipase Cβ; IP3 and DAG

Q5. Receptor desensitization of GPCRs commonly involves which kinases and scaffold proteins?

  • RTKs and SH2 proteins
  • GRKs and arrestins
  • PKC and calmodulin
  • MAPKs and 14-3-3 proteins

Correct Answer: GRKs and arrestins

Q6. What does biased agonism at a GPCR refer to?

  • A ligand that only binds irreversibly
  • Preferential activation of specific downstream pathways (e.g., G protein vs arrestin)
  • An agonist that is also an enzyme inhibitor
  • A ligand that blocks orthosteric and allosteric sites equally

Correct Answer: Preferential activation of specific downstream pathways (e.g., G protein vs arrestin)

Q7. The orthosteric binding site of a GPCR is defined as:

  • The intracellular G-protein interaction site
  • The site where endogenous ligand binds
  • A distal regulatory phosphorylation site
  • A site that exclusively binds ions

Correct Answer: The site where endogenous ligand binds

Q8. Which term describes a ligand that reduces the constitutive activity of a receptor?

  • Partial agonist
  • Inverse agonist
  • Neutral antagonist
  • Positive allosteric modulator

Correct Answer: Inverse agonist

Q9. Besides blocking G-protein coupling, beta-arrestins also mediate which process?

  • Direct activation of adenylate cyclase
  • Receptor internalization and arrestin-dependent signaling
  • Ubiquitin-independent membrane fusion
  • Phospholipid synthesis

Correct Answer: Receptor internalization and arrestin-dependent signaling

Q10. Which of the following receptors is a classical GPCR?

  • Nicotinic acetylcholine receptor
  • Insulin receptor
  • β2-adrenergic receptor
  • NMDA receptor

Correct Answer: β2-adrenergic receptor

Q11. What molecular event on the Gα subunit directly leads to GPCR signal termination?

  • Binding of GDP instead of GTP
  • Exchange of GDP for GTP
  • Hydrolysis of bound GTP to GDP
  • Phosphorylation of Gα by GRKs

Correct Answer: Hydrolysis of bound GTP to GDP

Q12. RGS proteins modulate GPCR signaling by which mechanism?

  • Acting as guanine nucleotide exchange factors (GEFs)
  • Acting as GTPase-activating proteins (GAPs) to accelerate Gα GTP hydrolysis
  • Phosphorylating GPCRs to promote arrestin binding
  • Blocking ligand binding at the orthosteric site

Correct Answer: Acting as GTPase-activating proteins (GAPs) to accelerate Gα GTP hydrolysis

Q13. Increased intracellular cAMP most directly activates which effector kinase?

  • Protein kinase C (PKC)
  • Protein kinase A (PKA)
  • MAP kinase (ERK)
  • Calcium/calmodulin-dependent kinase (CaMK)

Correct Answer: Protein kinase A (PKA)

Q14. Phospholipase C hydrolyzes PIP2 to generate which two second messengers?

  • DAG and IP3
  • cAMP and cGMP
  • Arachidonic acid and prostaglandin
  • ATP and ADP

Correct Answer: DAG and IP3

Q15. IP3-mediated signaling primarily leads to which intracellular outcome?

  • Activation of adenylate cyclase
  • Release of Ca2+ from endoplasmic reticulum stores
  • Direct phosphorylation of membrane receptors
  • Synthesis of cGMP

Correct Answer: Release of Ca2+ from endoplasmic reticulum stores

Q16. A molecule that binds a GPCR at a different site than the endogenous ligand and modulates its response is called:

  • An orthosteric antagonist
  • An allosteric modulator
  • A competitive agonist
  • A covalent agonist

Correct Answer: An allosteric modulator

Q17. In radioligand binding studies, which parameter is used to estimate receptor density (total number of binding sites)?

  • Kd (dissociation constant)
  • Bmax
  • EC50
  • IC50

Correct Answer: Bmax

Q18. Constitutive activity of a GPCR means:

  • The receptor only signals when ligand is present
  • The receptor signals in the absence of ligand
  • The receptor is permanently internalized
  • The receptor cannot couple to G proteins

Correct Answer: The receptor signals in the absence of ligand

Q19. GPCR oligomerization (dimerization/multimerization) can affect which of the following?

  • Ligand selectivity, signaling efficacy and trafficking
  • Only transcriptional regulation
  • Only extracellular matrix binding
  • Only enzymatic cleavage of ligands

Correct Answer: Ligand selectivity, signaling efficacy and trafficking

Q20. Which experimental assay is most appropriate to quantify a GPCR-mediated increase in intracellular cAMP?

  • Radioligand binding assay
  • cAMP accumulation assay (functional assay)
  • SDS-PAGE protein gel
  • Genomic PCR

Correct Answer: cAMP accumulation assay (functional assay)

Q21. Arrestin-dependent signaling downstream of GPCRs is best described as:

  • G-protein-independent signaling scaffold that activates kinases such as ERK
  • Direct activation of adenylate cyclase
  • Inhibition of all intracellular kinases
  • Transcriptional activation in the nucleus only

Correct Answer: G-protein-independent signaling scaffold that activates kinases such as ERK

Q22. Which drug is a classic non-selective β-adrenergic receptor antagonist used in cardiovascular disease?

  • Propranolol
  • Metoprolol
  • Atenolol
  • Dobutamine

Correct Answer: Propranolol

Q23. The β1-adrenergic receptor primarily couples to which G protein class?

  • Gi
  • Gq
  • Gs
  • G12/13

Correct Answer: Gs

Q24. G-protein receptor kinases (GRKs) typically phosphorylate which amino acid residues on GPCRs?

  • Tryptophan and tyrosine
  • Serine and threonine
  • Alanine and glycine
  • Histidine and lysine

Correct Answer: Serine and threonine

Q25. Receptor internalization via clathrin-coated pits is commonly initiated by which interaction?

  • Direct G-protein binding to clathrin
  • Arrestin binding to phosphorylated receptors
  • Orthosteric ligand binding to intracellular loop
  • Ubiquitination of ligand

Correct Answer: Arrestin binding to phosphorylated receptors

Q26. A molecule that increases the efficacy of the orthosteric ligand when binding at a separate site is called:

  • Negative allosteric modulator (NAM)
  • Neutral antagonist
  • Positive allosteric modulator (PAM)
  • Inverse agonist

Correct Answer: Positive allosteric modulator (PAM)

Q27. Which investigational μ-opioid receptor ligand was developed as a G-protein-biased agonist to reduce respiratory depression?

  • Morphine
  • Oxycodone
  • Oliceridine (TRV130)
  • Naloxone

Correct Answer: Oliceridine (TRV130)

Q28. In pharmacology, the term ‘efficacy’ refers to:

  • The affinity of a drug for its receptor
  • The ability of a bound ligand to produce a maximal response
  • The rate of ligand-receptor dissociation
  • The plasma concentration of a drug

Correct Answer: The ability of a bound ligand to produce a maximal response

Q29. Which technique can detect real-time conformational changes or protein–protein interactions of GPCRs in live cells?

  • Western blot
  • Radioligand saturation binding
  • FRET/BRET-based biosensors
  • Mass spectrometry of fixed tissue

Correct Answer: FRET/BRET-based biosensors

Q30. Antagonists of the dopamine D2 receptor are primarily used clinically to treat which condition?

  • Type 2 diabetes
  • Schizophrenia
  • Hypertension
  • Asthma

Correct Answer: Schizophrenia

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