LO’s Batny Taujany
Pharmacology- Drug receptors
Describe the major types of target proteins on which drugs act.
There are four major types of target proteins on which drugs act: receptors, ion channels, enzymes and
carrier molecules.
1. Receptors
Sensing elements in the chemical communication system that coordinate all the different cells in the body.
4 main receptor types:
 Ligand-gated ion channels (ionotropic receptors) – transmembrane ion channel which incorporate
a receptor, and when open that receptor is occupied by an agonist. Extremely rapid cell activation
with a time scale of milliseconds. Eg. Ach, Glycine.
 G-protein coupled receptors (metabotropic receptors) – transmembrane receptors that sense
molecules extracellular and in turn activate intracellular pathways. Effector is either a channel or
enzyme, but more commonly an enzyme. Slow cell activation with a time scale of seconds. Eg.
Muscarininc ACh, adrenoceptors.

Kinase-linked receptors – transmembrane and targets protein kinases. Cell activation with a time
scale of minutes to hour. These receptors consist of an extracellular hormone binding domain and a
cytoplasmic enzyme domain. Enzyme is usually a protein tyrosine kinase.
 Nuclear receptors (intracellular receptors) – intracellular, effector is gene transcription via DNA
coupling. Eg. Sex steroids (testosterone), vitamins (vitamin D).
2. Ion channels
 Voltage-gated ion channels- transmembrane located, opens when cell membrane depolarises.
3. Enzymes
 The drug is often structurally similar to the substrate and acts as a competitive inhibitor of the
enzyme.
 Drugs may bind irreversible and non-competitive.
4. Transporters (carriers)
 Symports and antiports
 Integral membrane proteins
 Can assist in transport via facilitated diffusion or active transport
Describe the structure and activity of receptors and ion channels
Ligand-gated ion
G-protein coupled
Kinase-linked
channels
receptors
receptors
Nuclear receptors
Location
transmembrane
transmembrane
transmembrane
intracellular
Effector
Ion channel
Channel or enzyme
Protein kinases
Gene transcription
Coupling
Direct
G-protein
Direct
via DNA
Timescale
Extremely rapid cell
activation (milliseconds)
Slow cell activation
(seconds)
Activation (minuteshours)
Cell activation
(hours)
Examples
Nicotinic acetylcholine
(Ach)
GABA
Excitatory amino acids (eg
NMDA, aspartate)
Glycine
Muscarinic Ach
Adrenoceptors
Insulin
Growth factors (eg.
Nerve growth factor)
Cytokine receptors (eg.
Interferon-gamma).
Sex steroids
Glucocorticoids
Mineralocorticoids
Hormones and
vitamins
LO’s Batny Taujany
Describe the various forms of receptor-effector linkages.
LIGAND-GATED ION CHANNELS - IONOTROPIC
Nicotinic ACh Receptor
 5 subunits (alpha, gamma, alpha, beta, delta) - form a pore in the membrane
 Activation requires 2 ACh molecules bind 2 alpha subunits –conformational change –channel
opens.
 Allows passage of Na+, K+, Ca2+ G-PROTEIN COUPLED RECEPTORS – METABOTROPIC Many extracellular ligands act by increasing intracellular concentration of second messengers
Principle 2nd messengers: cAMP, Ca2+, Phosphoinositides.
Role of G-Proteins
 G-proteins recognise activated GPCRs and communicate to effector system
 3 subunits – α β γ anchored to membrane
 Coupling of α-subunit to an agonist-occupied receptor causes bound GDP to be replaced by GTP
 α-GTP complex dissociates from receptor and the β γ complex
 α-GTP complex can then interact with a target protein (enzyme or ion channel)
 β γ complex may also activate a target protein
 GTP-ase activity of α-subunit increases when bound to a target – leading to hydrolysis of bound
GTP back to GDP + P
 α then reunites with β γ complex
 Specificity is due to molecular variation of alpha subunit (> 20 subtypes)
 G proteins may be inhibitory or stimulatory Targets for G-Proteins
 Adenylate cyclase/cAMP system
 Phospholipase C/inositol phosphate system
 Regulation of ion channels KINASE-LINKED RECEPTORS
 Extracellular hormone binding domain and a cytoplasmic enzyme domain.
 Enzyme is usually protein tyrosine kinase (serine kinase or guanyl cyclase).
 Hormone Binding
NUCLEAR RECEPTORS
Agonist-receptor complex acting on DNA results in either:
 Transcription and translation of mediator proteins
 Repression of expression of certain genes with inhibition of production of specific proteins.