Topic of receptors is also of prime importance while
preparing for the GPAT exam. Every year, you will find 1-2 questions from this
section. Most of the student neglect this topic as it is one of the least
taught topics in the classes. Here I am discussing this topic in detail to have
you a comprehensive understanding of the topic.
It was Paul ehlrich who coined the term receptor. The
molecules which have affinity for the receptors and have intrinsic activity or
efficacy are termed as agonists. On the other hand, molecules which lack
intrinsic activity/efficacy but do possess affinity are called antagonists. Inverse
agonists neither has a typical agonist activity nor of a typical antagonist. It
produces the activity totally opposite of agonist. Together, agonist,
antagonist and inverse agonists are called ligands (Compounds having affinity
to the receptors).
Types of receptors
Basically receptors are divided into five types depending on
their mechanism of action and types of response. Here is the detail of each
type of receptor:
Transmembrane ion channels
Transmembrane ion channels are further classified into of
two types-
a) Ligand gated ion channels- These are the receptors which
produce most rapid response. Examples of
ligand gated ion channels include- Nicotinic receptors (Ach), GABA, Glycine and
Glutamate.
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Ligand gated ion channels. This image can be used only by giving a link to this article |
Let us study these receptors with the example of Ach on
nicotinic receptors. Nicotinic receptors are consist of 5 subunits – 2 α and 3 different combination of α,β,ϒ and δ subunits. First Ach binds to 2
α subunits which brings out the conformational change in ligand gate. This
result in the opening of the receptor from the centre and entry of Na+
in ECF occurs. This ultimately results in the depolarization of surrounding
plasma protein and ultimately the response.
b) Voltage gated
& 2nd messenger gated ion channels- Most common example of
voltage gated channels include the Na+ channels responsible for
impulse conduction in sensory nerve fibres that transmit information about pain
and temperature (protonated lidocaine blocks the Na+ channels from ICF).
Ca2+
and K+ pumps or channels are example of 2nd messenger.
Transmembrane G protein coupled receptors (GPCR)
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G protein coupled receptor. This image can be used only by giving a link to this article |
Close to the
carboxy terminus, serine & threonine residues are also present which are
responsible for ATP dependent phosphorylation. Following long activation of the
receptors, phosphorylation of these areas occurs and results in the
inactivation of the receptors.
There are more
than one GPCR for a single ligand. e.g. Noradrenaline has 9 different
adrenergic receptors.
G proteins- G proteins are heterotrimeric in nature
with α, β & ϒ subunits. At least there are 13 G proteins which are divided
into four groups-
i) Gs proteins-
Stimulates adenyl cyclase activity & Ca2+ channels.
ii) Gi
proteins- Decrease adenyl cyclase & increase K+ channels.
iii) Gq
proteins- Increase phospholipase C activity.
iv) G12
proteins- Modulate Na+/H+ ion exchanger.
Mechanism of action of GPCR proteins
After the binding
of ligand, GPCR activates and which results in the conformational change in
linked G protein. This result in the release of GDP associated with α subunit
of G protein. GDP is replaced by the GTP and α-GTP complex is formed and
dissociated from the αβ subunit which ultimately binds to target enzyme. This
results in activation/inhibition of the target enzyme.
Within the short
duration of time, α subunit catalyse the dephosphorylation of GTP to GDP and
reassociation of α subunit with αβ subunit occurs and this ultimately results
in the inactivation of G protein.
Only variation to
this scheme is the activation of G protein gated channels by αβ subunits.
i) Second
messenger pathway-
Magnitude of the response is directly proportional to the concentration of cAMP. Degradation of cAMP is done by the phosphodiesterase or by active transport out of the cell. Similar pathway is for the cGMP (ANF & NO). One effect of this pathway is relaxation of smooth muscles by dephosphorylation of myosin light kinase.
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Second messenger pathway of GPCR. This image can be used only by giving a link to this article |
Magnitude of the response is directly proportional to the concentration of cAMP. Degradation of cAMP is done by the phosphodiesterase or by active transport out of the cell. Similar pathway is for the cGMP (ANF & NO). One effect of this pathway is relaxation of smooth muscles by dephosphorylation of myosin light kinase.
ii) IP3/DAG
pathway-
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IP3/DAG pathway of GPCR. This image can be used only by giving a link to this article |
Transmembrane catalytic receptors
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Transmembrane catalytic receptors. This image can be used only by giving a link to this article |
Mainly peptide hormones including Insulin, EGF, PDGF & ANF acts through this pathway. Extracellular portion is for ligand binding while intracellular portion of the receptor possess enzymatic activity (kinase activity).
Enzyme coupled receptors
These receptors
are similar to the catalytic receptors except their intracellular portion don’t
have enzymatic activity instead they have combine with other enzyme.
Examples include
cytokines, erythropoietin & interferrons. Enzymes linked are bound enzymes
of Janus kinase family (JAK). JAK phosphorlylates ligand bound receptors. The
phosphorylated receptors then bind other molecules called signal transducers
& activators of transcriptions (STATs).
STATs are also
phosphorylated by JAKs & dissociated into cytoplasm. STATs from cytoplasm
enters nucleus and results in the gene transcription.
Interacellular cytoplasmic/Nuclear receptors
Receptors are
present in cytoplasm or at nucleus membrane. Receptors activated only by lipid
soluble ligands that can diffuse cell membrane. Examples include steroid
hormones, Vitamin K and NO.
Carboxy terminus
of the receptor binds with ligand whereas amino terminus is the site for heat
shock protein-90.
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