Makindo Medical Notes

🔗 G Protein-Coupled Receptors (GPCRs) are a huge family of cell surface receptors that convert outside signals → inside responses through G proteins. They regulate vision 👁️, smell 👃, mood 🧠, heart ❤️, and immunity 🦠 — making them one of the most important drug targets in medicine 💊.

🧩 Structure of GPCRs

• 7 transmembrane α-helices ➿
• Extracellular N-terminus & intracellular C-terminus
• 3 extracellular + 3 intracellular loops

⚙️ Mechanism of GPCR Activation

• 🎯 Ligand binding → hormone/neurotransmitter/drug attaches to receptor.
• 🔄 G protein activation → GDP on α-subunit swapped for GTP.
• 📡 Signal transduction → α and βγ subunits regulate enzymes/ion channels.
• 🛑 Termination → GTP hydrolysed → receptor resets.

🔬 Types of G Proteins (α-subunits)

• 📈 Gs: stimulates adenylate cyclase → ↑ cAMP
• 📉 Gi: inhibits adenylate cyclase → ↓ cAMP
• 💥 Gq: activates PLC → IP₃ + DAG → Ca²⁺ signalling
• 🔧 G12/13: cytoskeletal control & migration

🌟 Functions of GPCRs

• 👁️👃👅 Sensory: vision (rhodopsin), smell (olfactory), taste receptors
• 🧠 Neurotransmission: dopamine, serotonin, acetylcholine
• 🦠 Immune response: chemokine receptors guide cell migration
• 🌱 Growth & differentiation: regulate proliferation
• ❤️ Cardiovascular: adrenergic receptors control HR & BP

🏥 Clinical Relevance

• 💊 Pharmacological targets:
  • Beta-blockers → adrenergic GPCRs
  • Antipsychotics → dopamine GPCRs
  • Antihistamines → histamine GPCRs
• 🧬 Genetic mutations → cancer, congenital syndromes, metabolic disease
• 🚀 Drug development → ~30–40% of all drugs act on GPCRs

📌 Summary

GPCRs = the master switches of cell communication. They sense extracellular cues and trigger intracellular cascades through G proteins. Because of their central role in physiology and disease, GPCRs remain one of the hottest targets in modern therapeutics 💊🔬.