Pharmacodynamics: Drug Receptors

DRUG RECEPTORS
• These are macromolecules of cells that combine
chemically with drugs
• The drug must have complementary chemical
components to interact with specific receptor.
Therefore, receptors provide a means of selective
action of drugs
• When drugs interact with receptors, they usually
produce altered configuration or charge distribution
 Drug Receptors

• In many cases when drugs interact with

receptors, intermediate products are formed
(called second messengers) and these activate
the tissue/organ response to the drug.
• The process of formation of the intermediate
products is called Transduction process.
 Categories of Receptors
• Type 1: Channel-linked receptors or
ionotropic receptors. They are membrane
receptors coupled directly to ion channels.
They are activated by nerve transmitters
(neurotransmitters) which initiate fast action
e.g. acetylcholine on nicotinic receptors at
autonomic ganglia & neuromuscular junction.
 Type-1 receptors continued
• Chemically, these receptors are proteins with
20 transmembrane helical segements
(consisting of 2a,b,g,d subunits) arranged
around a central aqueous channel.
• When the drug binds to the receptor, the
channel opens within milliseconds and ions
enter the cell cytoplasm and trigger an
appropriate tissue/organ response.
 Type-2: G-protein coupled receptor
• These are also called metabotropic receptors.
• They are membrane receptors coupled via a G-
protein (guanine linked protein) to a intracellular
effector system.
• Chemically, the receptor consists of a single
polypeptide chain of 400-500 amino acid residues
arranged in 7 transmembrane helices with the NH
terminal extracellularly and the carboxy terminal
intracellularly. The G-protein binds close to the
intracellular terminal.
• These are receptors of hormones and slow
neurotransmitters ( norepinephrine etc).
 Role of G-protein coupled receptor
• When an agonist binds to the receptor, a
conformational change occurs at the cytoplasmic
domain (segment) of the receptor. The affinity for the
G-protein at this site increases and it binds to the
receptor and activates or inhibits specific enzymes
leading to production of a second messenger (cAMP,
IP3 ); this is the transduction process
 Classes of G-proteins & examples of
effects on enzyme systems
• There are three main classes of G-protein: Gs-
stimulates/activates; Gi – inhibits; Gq – activates
specific enzymes.
• Enzyme systems involved: Gsand Gi proteins act on
adenylate cyclase to affect the production of cAMP
from ATP; Gq protein acts on Phospholipase –C which
increases the production of IP3 (inositol
triphosphate)and DAG (diacylglycerol) from PIP2
(phosphoinositol biphosphate).
 Type-3: Tyrosine kinase & Guanylate
cyclase linked receptors
• These are cell membrane receptors which
incorporate an intracellular protein kinase (or
cyclase ) domain. Usually, the kinase is linked
to a tyrosine residue.
• The tyrosine kinase receptors mediate the
activity of growth factors, cytokines,
hormones (insulin). The guanylate cyclase
receptors mediate activity of atrial natriuretic
peptide.
 Type-4: Receptors that regulate Gene
transcription
• These are nuclear receptors, but some are
occasionally located in the cytoplasm before
translocation into the nucleus
• They regulate DNA transcription and they are
activated by steroid and thyroid hormones
• They are also activated by some lipid soluble
compounds; these can cause genetic mutations