Receptors in the Body

On pharmacodynamics, because receptors are the primary molecular targets through which drugs act to produce physiological effects.

These are organized all major receptor classes in the human body by superfamily, with examples, functions, and signaling mechanisms.

OVERVIEW OF RECEPTOR SUPERFAMILIES

Pharmacodynamics divides receptors into four major classes based on signal transduction mechanisms:

Class	Location / Speed	Signal Mechanism	Examples	Response Time
1️⃣ Ion channel–linked receptors (ligand-gated ion channels)	Cell membrane	Ion flux changes membrane potential or [Ca²⁺], [Na⁺], [Cl⁻], [K⁺]	Nicotinic ACh, GABA-A, NMDA	Milliseconds
2️⃣ G protein–coupled receptors (GPCRs)	Cell membrane	Activates G proteins → second messengers (cAMP, IP₃, DAG, Ca²⁺)	Adrenergic, Muscarinic, Dopamine, Serotonin	Seconds
3️⃣ Enzyme-linked receptors (usually tyrosine kinases)	Cell membrane	Ligand binding → dimerization → autophosphorylation → MAPK/PI3K pathways	Insulin, EGFR, VEGFR	Minutes to hours
4️⃣ Nuclear receptors (gene transcription regulators)	Cytoplasm/nucleus	Ligand binds → transcription modulation	Steroid hormones, thyroid hormone, vitamin D	Hours to days

1. ION CHANNEL–LINKED RECEPTORS (Ligand-Gated Ion Channels)

Mechanism:
Ligand binds → channel opens → ion influx or efflux → depolarization/hyperpolarization → cell response.

Receptor	Endogenous Ligand	Ion Conductance	Main Function	Drugs / Modulators
Nicotinic acetylcholine receptor (nAChR)	Acetylcholine	Na⁺, K⁺	Skeletal muscle contraction, autonomic ganglia transmission	Succinylcholine, Nicotine, Curare
GABA-A receptor	GABA	Cl⁻ influx	Inhibitory neurotransmission (hyperpolarization)	Benzodiazepines, Barbiturates
Glycine receptor	Glycine	Cl⁻ influx	Spinal inhibitory neurotransmission	Strychnine (antagonist)
NMDA receptor (Glutamate)	Glutamate + Glycine	Ca²⁺, Na⁺ influx	Memory, learning, excitatory signaling	Ketamine, PCP
AMPA receptor (Glutamate)	Glutamate	Na⁺ influx	Fast excitatory neurotransmission
5-HT3 receptor	Serotonin	Na⁺, K⁺	GI motility, emesis	Ondansetron (antagonist)

2. G PROTEIN–COUPLED RECEPTORS (GPCRs)

Mechanism:
Ligand binds → G protein (Gs, Gi, or Gq) activation → second messenger system → effector response.

G Protein Type	Second Messenger	Effect
Gs	↑ cAMP (via adenylate cyclase)	Activates PKA → ↑ Ca²⁺ influx, ↑ heart rate
Gi	↓ cAMP	Inhibits PKA → ↓ heart rate, neuronal inhibition
Gq	↑ IP₃/DAG → ↑ intracellular Ca²⁺	Smooth muscle contraction, secretion

Common GPCR Receptors:

Receptor	G Protein	Major Function	Example Drugs
β₁, β₂, β₃ adrenergic	Gs	↑ HR, bronchodilation, lipolysis	Epinephrine, Albuterol
α₂ adrenergic	Gi	↓ NE release (autoreceptor)	Clonidine
α₁ adrenergic	Gq	Vasoconstriction (smooth muscle)	Phenylephrine
Muscarinic M₁, M₃, M₅	Gq	↑ Gland secretion, smooth muscle contraction	Pilocarpine
Muscarinic M₂, M₄	Gi	↓ HR, ↓ contractility	Atropine (antagonist)
D₁, D₅ dopamine	Gs	Vasodilation (renal), ↑ cAMP	Dopamine
D₂, D₃, D₄ dopamine	Gi	↓ Prolactin release, reward pathway	Haloperidol
H₁ histamine	Gq	Allergy, vasodilation, bronchoconstriction	Diphenhydramine
H₂ histamine	Gs	↑ Gastric acid secretion	Ranitidine
5-HT1	Gi	Vasoconstriction	Triptans
5-HT2	Gq	Platelet aggregation, vasoconstriction	LSD (agonist), Ketanserin (antagonist)
5-HT4,6,7	Gs	↑ GI motility, CNS effects	Metoclopramide
Opioid receptors (μ, κ, δ)	Gi	Analgesia, sedation, euphoria	Morphine, Fentanyl

3. ENZYME-LINKED RECEPTORS

Mechanism:
Ligand binds → receptor dimerizes → autophosphorylation → recruits signaling proteins → downstream cascades (MAPK, PI3K-Akt, JAK-STAT).

Receptor	Ligand	Main Function	Pathway Activated
Insulin receptor (RTK)	Insulin	Glucose uptake, metabolism	PI3K-Akt, MAPK
EGFR (Epidermal Growth Factor Receptor)	EGF	Cell growth, proliferation	MAPK
VEGFR	VEGF	Angiogenesis	PLCγ–PKC
PDGFR	PDGF	Cell growth	MAPK
Cytokine receptors (non-RTK, use JAK-STAT)	ILs, Interferons, GH	Immune modulation, growth	JAK-STAT
Guanylyl cyclase-linked receptors	ANP, NO (soluble form)	Vasodilation	↑ cGMP

4. NUCLEAR (INTRACELLULAR) RECEPTORS

Mechanism:
Lipophilic ligand enters cell → binds cytosolic or nuclear receptor → receptor-ligand complex binds DNA at hormone response elements → regulates gene transcription.

Receptor Type	Ligands	Location	Function
Steroid hormone receptors	Cortisol, Aldosterone, Estrogen, Progesterone, Testosterone	Cytoplasm → Nucleus	Gene expression for metabolism, reproduction
Thyroid hormone receptor (TR)	T₃, T₄	Nucleus	Basal metabolic rate control
Vitamin D receptor	Calcitriol	Nucleus	Calcium/phosphate homeostasis
Retinoic acid receptor (RAR)	Retinoids (Vitamin A derivatives)	Nucleus	Cell differentiation

5. OTHER RECEPTOR TYPES / TARGETS IN PHARMACODYNAMICS

Target Type	Examples	Mechanism
Transporters	SERT, NET, DAT	Reuptake inhibition (SSRIs, cocaine)
Enzymes	ACE, MAO, COX	Enzyme inhibition (captopril, NSAIDs)
Ion channels (voltage-gated)	Na⁺, Ca²⁺, K⁺ channels	Blockade or opening alters excitability (lidocaine, verapamil)
Structural proteins	Tubulin (colchicine, vincristine)	Inhibit microtubule function
DNA / RNA	Anticancer or antiviral drugs	Inhibit replication or transcription

Simplified Mnemonic Summary

Receptor Type	Signal Molecule	Time Course	Example
Ion channel	Ions (Na⁺, K⁺, Cl⁻, Ca²⁺)	Milliseconds	GABA-A
GPCR	G proteins (cAMP, IP₃, DAG)	Seconds	β-Adrenergic
Enzyme-linked	Kinase cascades	Minutes	Insulin
Nuclear	Gene transcription	Hours–days	Cortisol