Receptor

In the Name of Allah, the
Beneficent, the Most Merciful
RECEPTOR BY DR.MOHAMMED ABDUL RAOF

GOOD MORNINGRECEPTOR BY DR.MOHAMMED ABDUL RAOF

DR.MOHAMMED ABDUL RAOF
FIRST YEAR P.G. PHARMACOLOGY
D.C.M.S.

OVERVIEW
Definition of Receptor.
History on Receptor.
Stages of Receptor life-cycle.
Functions of Receptor.
Importance of Receptor studies.
Definition of Agonist, Antagonist & different types.
Definition of Affinity & Efficacy.
Types of Receptors.
Diseases associated due to Receptors.
Non-Receptor mediated mechanisms.
References.
Acknowledgements. RECEPTOR BY DR.MOHAMMED ABDUL RAOF

PAUL EHRLICH
“A DRUG WILL NOT WORK UNLESS IT IS BOUND”

RECEPTORS
IT IS DEFINED AS A REGULATORY
MACROMOLECULE MOSTLY PROTIENS OR BINDING
SITES LOCATED ON THE SURFACE OR INSIDE THE
EFFECTOR CELL THAT SERVES TO RECOGNIZE THE
LIGAND/SIGNAL MOLECULE /DRUG AND INITIATE
THE RESPONSE TO IT,BUT ITSELF HAS NO OTHER
FUNCTION.
RARELY,NUCLIEC ACIDS MAY ALSO SERVE AS
RECEPTORS.

RECEPTORS
LIGAND
EXOGENOUS
LIGANDS
-drugs
ENDOGENUS
LIGANDS
-hormones

Flow chart of agonist and receptor interaction

Drug receptor complex and effect

PAUL EHRLICH & JOHN LANGLEY
Coined the terms-RECEPTOR, DRUG,EFFECT & DRUG-RECEPTOR
COMPLEX
.

Earliest receptors to be identified were:
MUSCARINIC (BLOCKED BY ATROPINE)
NICOTINIC(BLOCKED BY CURARE)

Earliest receptors to be identified were:
MUSCARINIC (BLOCKED BY ATROPINE)
NICOTINIC(BLOCKED BY CURARE)
Now multiple subtypes have been further sub-
divided.
Stephenson’s modified theory was generally accepted
which states-
1.drug response depends on the affinity of a drug
for the receptors.
2.maximum dose is achieved even if a fraction of
receptors are unoccupied.

Every receptor exist in two interchangeable states:
Ra indicating ACTIVE
Ri indicating INACTIVE
Receptor discovery often begins by studying the
relations between structures and activities of a
group of drugs on some conveniently measured
response.
Cloning of new receptors by SEQUENCE
HOMOLOGY has identified a number of subtypes of
known receptor classes, such as-adrenoceptors and
serotonin receptors

STAGES OF RECEPTOR LIFE-CYCLE

TO PROPAGATE REGULATORY SIGNALS FROM
OUTSIDE TO INSIDE OF THE CELL.
TO INTERAGATE VARIOUS EXTRACELLULAR &
INTRACELLULAR REGULATORY SIGNALS.
TO AMPLIFY THE SIGNAL.
TO ADAPT TO SHORT TERM & LONG TERM
CHANGES IN REGULATING AND MAINTAINING
HOMEOSTASIS.
 THE RECEPTOR CONCEPT HAS IMPORTANT
PRACTICAL CONSEQUENCES IN DEVELOPMENT OF
DRUGS AND FOR ARRIVING AT THERAPEUTIC
DECISIONS IN CLINICAL PRACTICE.
FUNCTIONS OF RECEPTORS

ONE TYPE OF RECEPTOR CAN CAUSE VARIABLE ACTIVITY IN
VARIOUS CELL TYPES WITH VARIOUS DRUGS.

DUAL ROLE OF A RECEPTOR ACTIVITY

SAME DRUG CAUSE DIFFERENT RESPONSE
DEPENDING ON THE RECEPTORS

ONE DRUG CAN CREATE MULTIPLE
EFFECTS WITH ONE RECEPTOR

IMPORTANCE OF RECEPTOR STUDIES
RECEPTORS LARGELY DETERMINE THE QUANTITATIVE
RELATIONS BETWEEN DOSE OR CONCENTRATION OF A
DRUG AND ITS PHARMACOLOGIC EFFECTS.
RECEPTORS MEDIATE THE ACTIONS OF PHARMACOLOGIC
AGONISTS AND ANTAGONISTS.
RECEPTORS ARE RESPONSIBLE FOR SELECTIVITY OF DRUG
ACTION. THE MOLECULAR SIZE, SHAPE, AND ELECTRICAL
CHARGE OF A DRUG DETERMINE WHETHER—AND WITH
WHAT AFFINITY—IT WILL BIND TO A PARTICULAR RECEPTOR
AMONG THE VAST ARRAY OF CHEMICALLY DIFFERENT
BINDING SITES AVAILABLE IN A CELL, TISSUE OR PATIENT.

Targets for drug action
A drug is a chemical that affects physiological
function in a specific way.
EXCEPTIONS:-(on target proteins)
- enzymes
- carriers
- ion channels
-receptors
Specificy is reciprocal.
No drugs are completely specific.

PAUL EHRLICH said--
“A DRUG WILL NOT WORK UNLESS IT IS BOUND”

Binding of drugs to receptors
Obeys the law of mass action.
At equilibrium receptor occupancy is related to
drug concentration by the Langmuir’s equation.
The higher the affinity of the drug for the receptor,
the lower the concentration at which it produces a
given level of occupancy .
When two or more drugs compete for the same
receptors : each has the effect of reducing the
apparent affinity for the other.

RECEPTOR/AGONIST/ANTAGONIST

Ligand, agonist & antagonist

Drugs which alter the physiology of a cell by binding to
plasma membrane or intercellular receptors.
 a number of receptors must be occupied by agonists
before a measurable change in cell function occurs.
For example- a muscle cell does not depolarize simply
because one molecule of acetylcholine binds to a nicotinic
receptor and activates an ion channel.
AGONIST

TYPES OF AGONIST
Partial agonist is a drug which fails to produce
maximal effects, even when all the receptors are
occupied are occupied by the agonist.
Weak agonist must be bound to many more
receptors than a strong agonist to produce the
same effect.

Regulation of the activity of a receptor with conformation-selective drugs. Receptors
that have constitutive activity and are sensitive to inverse agonists include
benzodiazepine, histamine, opioid, cannabinoid, dopamine, bradykinin, and adenosine
receptors.

AGONIST AND INVERSE AGONIST

Presence of agonist and antagonist can
shift the graph

Relations between DRUG CONCENTRATION AND DRUG EFFECT (PANEL
A) OR RECEPTOR-BOUND DRUG(PANEL B).The drug concentrations at
which effect or receptor occupancy is half-maximal are denoted EC50 and KD
respectively.
EC50(EFFECTIVE CONCENTRATION 50%): The concentration of drug which induces at
least 50% to which the drug is administration. Then the specified clinical effect in
50% of the subject is seen.
Dissociation constant(KD):The dissociation constant is the measure of a drug’s
affinity for a given receptor.it is the concentration of drug required in solution to
achieve 50% occupancy of its receptors. Units are expressed in molar concentration.

Drug antagonism
Antagonist inhibit or block responses caused by agonist.
• Occurs by various mechanism:--
Chemical antagonism.
Pharmacokinetic antagonism.
Competitive antagonism.
Non competitive antagonism.
Physiological antagonism.
Irreversible antagonism.

ANTAGONIST

COMPETITIVE ANTAGONIST
COMPETES WITH AGONISTS FOR RECEPTORS.DURING
THE TIME THAT A RECEPTOR IS OCCUPIED BY AN
ANTAGONIST,AGONIST CANNOT BIND TO THE
RECEPTOR.
THE NUMBER OF RECEPTORS APPEARS UNCHANGED
BECAUSE HIGH DOSE OF AGONIST IS REQUIRED,IN THE
PRESENCE OF ANTAGONIST, TO ACHIEVE RECEPTOR
OCCUPANCY.THE ANTAGONISM CAN BE OVERCOME BY
HIGH DOSES OF AGONISTS.
ANTAGONIST AFFINITY, MEASURED IN THIS WAY
IS WIDELY USED AS A BASIS FOR RECEPTOR
CLASSIFICATION.

COMPETITIVE ANTAGONIST
REVERSIBLE COMPETITIVE ANTAGONISM HAVE TWO
MAIN CHARACTERISTICS OF ALL COMPETITIVE
ANTAGONISM:
1.IN THE PRESENCE OF ANTAGONIST ,THE AGONIST
LOG CONCENTRATION EFFECT CURVE IS SHIFTED TO
THE RIGHT WITHOUT CHANGE IN SLOPE/
MAXIMUM. THE EXTENT OF THE SHIFT BEING A
MEASURE OF THE DOSE RATIO.
2.DOSE RATIO INCREASES LINEARLY WITH THE
ANTAGONIST CONCENTRATION, THE SLOPE OF THIS
LINE IS A MEASURE OF THE AFFINITY OF THE
ANTAGONIST FOR THE RECEPTOR.

binds to a site other than the agonist-binding
domian.
Induces a conformational change in the receptor
such that the agonist no longer ‘recognizes’ the
agonist –binding domian.
Even high doses of agonist cannot overcome this
antagonism. Thus, it is considered to be
insurmountable.
The number of agonist-binding sites appears to be
reduced.
The affinity of agonist for the ‘unantagonized sites’
remain unchanged.
NON-COMPETITIVE ANTAGONIST:
RECEPTOR BY DR.MOHAMMED ABDUL
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IRREVERSIBLE ANTAGONIST(NON-EQUILIBRIUM COMPETITIVE):
Irreversible antagonists are also insurmountable.
These agents compete with agonists for the
agonist-binding domian.in contrast to competitive
antagonists-
They combine permanently with the receptor.
The rate of antagonism can be slowed by high
concentrations of agonist.
Once an irreversible antagonist binds to a particular
receptor, however, that receptor cannot be
reclaimed by an agonist.
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Agonists, antagonists and efficacy
Drugs acting on receptors may be agonists or antagonists.
AGONIST ANTAGONIST
INITIATES THE CHANGES IN CELL FUNCTION BY
PRODUCING EFFECTS IN CELL FUNCTION.
BINDS TO RECEPTORS WITHOUT INITIATING
SUCH CHANGES.
POTENCY DEPENDS ON EFFICACY IT’s EFFICACY IS ZERO
SHOW SELECTIVITY FOR ACTIVATED STATES SHOWS NO SELECTIVITY
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AFFINITY
AFFINITY:is the ability of a drug to bind with the
receptor and form a drug-receptor complex.it
doesn't guarantee response.
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EFFICACY
EFFICACY/INTRINSIC ACTIVITY: which means the
ability of a drug-receptor to trigger the
pharmacological response.
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Four receptor families on basis of molecular structure and the nature of
transduction mechanisms:
 1.ION-CHANNEL RECEPTORS (IONOTROPIC /LIGAND-BINDING)
 2.G-PROTIEN COUPLED RECEPTORS (METABOTROPIC
/SERPENTINE)
 3.KINASE LINKED RECEPTORS
 4.INTRA-CELLULAR RECEPTORS (CYTOSOLIC /NUCLEAR)
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AGONIST AT THE BINDING DOMIAN
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THESE RECEPTORS ARE LOCALISED ON CELL
MEMBRANE AND ARE COUPLED DIRECTLY TO
AN ION CHANNEL ARE ALSO CALLED AS LIGAND
GATED ION CHANNELS/RECEPTOR OPERATED
CHANNELS.
THE ONSET AND OFFSET OF RESPONSES IN
THIS RECEPTORS IS THE FASTEST OF A
MILLISECONDS IN A FAST SYNAPTIC
TRANSMISSIONS.
IT IS A CHANNEL WITH A RECEPTOR SITE THAT
AGONIST CAN OPEN THE CHANNEL,THE
ANTAGONIST PREVENTS THE AGONIST FROM
OPENING THE CHANNEL AND AN INVERSE
AGONIST CLOSES THE OPEN CHANNEL.
ION-CHANNEL RECEPTORS(IONOTROPIC )
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LIGAND GATED CHANNEL IN ACTION
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ION-CHANNEL RECEPTORS
GAMMA AMINO BUTYRIC ACID, 5HYDROXYTRYPTAMINE3,
NICOTINIC-CHOLINERGIC, GLYCINE, GLUTAMATE ARE
SOME OF THE RECEPTORS.
IN THESE RECEPTORS,AGONISTS DIRECTLY OPERATE THE
ION CHANNEL WITHOUT THE INTERVENTION BY ANY
COUPLING PROTIEN OR SECOND MESSENGER.
 THE BEST EXEMPLIFIED NICOTNIC-ACETYLCHOLINE
RECEPTOR OPERATED CHANNEL CONSISTS OF 5PROTIEN
SUBUNITS (2α+1β+1γ+1δ) ALL OF THEM PASS ACROSS THE
CELL MEMBRANE AND SURROND A CENTRAL
PORE.INORDER TO ACTIVATE THE RECEPTOR AND OPEN
THE CHANNEL ONE MOLECULE OF ACHETYLCHOLINE
SHOULD BIND TO EACH OF THE ALPHA SUBUNITS.ACTIVE
STATE BY OPENING THE PORE,OTHERWISE INACTIVE STATE
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The nicotinic acetylcholine (ACh) receptor, a ligand-gated ion channel. The receptor
molecule is depicted as embedded in a rectangular piece of plasma membrane, with
extracellular fluid above and cytoplasm below. Composed of five subunits (two α ,
one β , one δ , and one γ ), the receptor opens a central transmembrane ion channel
when ACh binds to sites on the extracellular domain of its subunits.
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AGONIST SHOULD BIND TO EACH OF THE ALPHA SUBUNITS.THE RECEPTOR REACHES
AN ACTIVE STATE BY OPENING THE PORE,OTHERWISE REMAINS IN INACTIVE
STATETHE BEST EXEMPLIFIED NICOTNIC-ACETYLCHOLINE RECEPTOR OPERATED
CHANNEL CONSISTS OF 5PROTIEN SUBUNITS(2α+1β+1γ+1δ) ALL OF THEM PASS
ACROSS THE CELL MEMBRANE AND SURROND A CENTRAL PORE.INORDER TO
ACTIVATE THE RECEPTOR AND OPEN THE CHANNEL ONE MOLECULE OF
ACHETYLCHOLINE
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G-PROTIEN COUPLED RECEPTORS
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Transmembrane topology of a typical serpentine receptor. The receptor's
cytoplasmic terminal tail contains numerous serine and threonine residues
whose hydroxyl (-OH) groups can be phosphorylated. This phosphorylation
may be associated with diminished receptor-G protein interaction.
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G protein in action
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GPCR ACTION
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GPCR IN ACTION
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G-PROTIEN COUPLED RECEPTORS(METABOTROPHIC)
large family of cell-membrane receptors that are
also called 7 pass receptors / 7 trans membrane /
serpentine receptors.
monomeric structure(rare-dimeric) with seven
trans membrane helices.
each receptor is present as a molecule of 7
αhelical units that have extra cellular attachment
for the drug, intracellular for the signal passage
and intercellular gtp activated proteins (G
proteins) for response effect.
amino terminus is outside the cell,carboxyisinside
the cell.
onset time of response is also in seconds.RECEPTOR BY DR.MOHAMMED ABDUL
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G-RECEPTOR IN ACTION
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GPCR AND ITS EFFECT
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G-PROTIEN COUPLED RECEPTORS
one receptor can be coupled to plenty of g- proteins.
some g-protein activate and others inhibit in signal
transduction.
examples are –
epinephrine, nor- epinephrine
purine,gaba,glutamate,opiods,vasopressin,
dopamine,5ht,histamine,adenosine,
muscarinic-acetylcholine….
 three major effector pathways—
--Adenyl cyclase
--Phospholipase c
--Channel regulation
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DOMINOES EFFECT OF ACTIVATED GPCR
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GPCR ACTIVATION EFFECTS
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G-PROTIEN CONTROLLED RECEPTOR FAMILIES
A FOURTH GROUP OF RECEPTORS FOR THE PHEROMONES WITH NO PHARMACOLOGICAL EFFECTS.
FAMILY RECEPTORS STRUCTURAL FEATURES
RHODOPSIN FAMILY LARGEST GROUP OF RECEPTORS FOR
MOST AMINE
NEUROTRANSMITTERS,PURINES,
NEUROPEPTIDES,PROSTANIODS,
CANNABINOIDS,….
SHORT EXTRACELLULAR AMINE
TAIL,LIGAND BINDS TO
TRANSMEMBRANE HELICES OR
TO EXTRA-CELLULAR LOOPS.
SECRETIN/GLUCAGON
RECERPTOR FAMILY
RECEPTORS FOR PEPTIDE
HORMONES INCLUDING
SECRETIN,GLUCAGON,CALCITONIN
INTERMEDIATE EXTRA-CELLULAR
TAIL,INCOOPERATING LIGAND-
BINDING DOMIAN.
METABOTROPIC
GLUTAMATE
RECEPTOR/CALCIUM
SENSOR FAMILY
SMALL GROUP:GABA RECEPTORS,
CALCIUM SENSING RECEPTORS,
METABOTROPIC GLUTAMATE
RECEPTORS
LONG EXTRACELLULAR TAIL,
INCOOPERATING LIGAND
BINDING DOMIAN
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Receptors coupled to G proteins (GPCRs) make up a family of "seven-transmembrane" (7-TM)
or "serpentine" receptors.
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DIFFERENT AGONIST ON GPCR
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DUAL ACTION OF GPCR RECEPTORS
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ADENYL CYCLASE - PATHWAY OF G-PROTIEN RECEPTORS
ACTIVATION OF THIS PATHWAY RESULTS IN
INTRACELLULAR ACCUMULATION OF SECOND
MESSENGER c-AMP WHICH FUNCTIONS MAINLY
THROUGH c-AMP DEPENDANT PROTIEN
KINASE(PKa).
THE Pka PHOSPHORYLATES & ALTERS THE
FUNCTION OF MANY ENZYMES,ION
CHANNELS,TRANSPORTERS & STRUCTURAL
PROTIENS.
INCREASED CONTRACTILITY/IMPULSE
GENERATION IN HEART.
RELAXES THE SMOOTH MUSCLES.
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GLYCOGENOLYSIS,LYPOLYSIS & INHIBITION OF
SECRETIN/MEDIATOR RELEASE.
MODULATION OF JUNCTIONAL
TRANSMISSION,HORMONE SYNTHESIS.
OPENS Ca2+ CHANNEL IN HEART,BRAIN & KIDNEY,
CALLED AS CYCLIC NUCLEOTIDE GATED
CHANNEL(CNG)
ADENYL CYCLASE IS INHIBITED THROUGH
INHIBITORY Gi-protien.
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GPCR C-AMP
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ADENYL CYCLASE -- PATHWAY OF G-PROTIEN RECEPTORS
The cAMP second messenger pathway. Key proteins include hormone receptors (Rec), a
stimulatory G protein (Gs), catalytic adenylyl cyclase (AC), phosphodiesterases (PDE) that
hydrolyze cAMP, cAMP-dependent kinases, with regulatory (R) and catalytic (C) subunits,
protein substrates (S) of the kinases, and phosphatases (P'ase), which remove phosphates
from substrate proteins. Open arrows denote regulatory effects.
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↑/CONTRACTION role/ACTIVATION ↓/RELAXATION role/INHIBITION
Adrenergic-β Adrenergic-α2
Histamine-H2 Muscarinic-M2
Dopamine-D1 Dopamine-D2
Glucagon 5-HT1
FSH & LH GABAB
ACTH O
TSH A-AT
Prostaglandin-EP2 Prostaglandin-EP3
Prostacyclin-IP Somatostatin
Adenosine-A2 Adenosine-A1
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PHOSPHOLIPASE C--PATHWAY OF G-PROTIEN RECEPTORS
 ACTIVATION OF PHOSPOLIPASE C (PLc) HYDROLYSES THE MEMBRANE
PHOSPHOLIPID PHOSPHATIDYL INOSITOL4,5-BIPHOSPATE(PIP2) TO
GENERATE SECOND MESSENGER INOSITOL1,4,5-TRIPHOSPHATE(IP3)
& DIACYLGLYCEROL(DAG).
 THE IP3 MOBILIZES CA2+ FROM INTRACELLULAR DEPOTS.
 DAG ENHANCES PROTIEN KINASE C (PKc) ACTIVATION BY CA2+ AND
CALMODULIN(CAM).
 CAM,PKc AND OTHER EFFECTORS –MEDIATES/MODULATES
CONTRACTION,SECRETION,TRANMITTER RELEASE,EICOSANIOD
SYNTHESIS,NEURONAL EXCITABILITY,INTRACELLULAR MOVEMENTS,
MEMBRANE FUNCTION,METABOLISM,CELL PROLIFERATION…
 PLc CAN BE INHIBITED BY INHIBITORY Gi PROTIEN.
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PHOSPHOLIPASE C--PATHWAY OF G-PROTIEN RECEPTORS
The Ca2+-phosphoinositide signalling pathway. Key proteins include hormone receptors (R), a
G protein (G), a phosphoinositide-specific phospholipase C (PLC), protein kinase C substrates of
the kinase (S), calmodulin (CaM), and calmodulin-binding enzymes (E), including kinases,
phosphodiesterases, etc. (PIP2, phosphatidylinositol-4,5-bisphosphate; DAG, diacylglycerol.
Asterisk denotes activated state. Open arrows denote regulatory effects.)
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PHOSPHOLIPASE C - PATHWAY OF G-PROTIEN RECEPTORS
RECEPTORS WITH PHOSPOLIPASE IP 3-DAG PATHWAY:
ADRENERGIC-α1
HISTAMINE-H1
MUSCARINIC-M1,M3
5-HT2
VASOPRESSIN-OXYTOCIN
BRADYKININ-B2
ANGIOTENSIN-AT1
PROSTAGLANDIN-FP,EP1,EP3.
THROMBOXANE-TP
LEUKOTRIENE
CHOLECYSTOKININ-GASTRIN
PAF
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CHANNEL REGULATION- PATHWAY OF G-PROTIEN RECEPTORS
 THE ACTIVATED G-PROTIENS CAN ALSO OPEN OR CLOSE IONIC
CHANNELS SPECIFIC FOR Ca2+,K+ OR Na+ WITHOUT THE
INTERVENTION OF ANY SECOND MESSENGER LIKE Camp or ip3 AND
BRING ABOUT HYPERPOLARIZATION/DEPOLARIZATION/CHANGES IN
INTRACELLULAR Ca2+
 Gs OPENS CALCIUM CHANNELS IN MYOCARDIUM & SKELETAL
MUSCLES.
 Gi & Go OPENS POTASSIUM CHANNELS IN HEART & SMOOTH
MUSCLES.
 PHYSIOLOGICAL RESPONSES LIKE CHANGES IN INOTROPY,
CHRONOTROPY,TRANSMITTER RELEASE,NEURONAL ACTIVITY,
SMOOTH MUSCLE RELAXATION IS ENABLED.
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CHANNEL REGULATION- PATHWAY OF G-PROTIEN RECEPTORS
Ca2+↑ Ca2+↓ K+↑
ADRENERGIC-β1
(heart, skeletal muscle)
DOPAMINE-D2 ADRENERGIC-α2
GABAB MUSCARINIC-M2
OPIOD-κ DOPAMINE-D2
ADENOSINE-A1 5-HT1A
SOMATOSTATIN GABAB
OPIOD-µ,δ
ADENOSINE-A1
THE ACTIVATED G-PROTIENS CAN ALSO OPEN OR CLOSE IONIC CHANNELS SPECIFIC FOR Ca2+,K+
OR Na+ WITHOUT THE INTERVENTION OF ANY SECOND MESSENGER LIKE Camp or ip3 AND
BRING ABOUT HYPERPOLARIZATION/DEPOLARIZATION/CHANGES IN INTRACELLULAR Ca2+
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TYROSINE RECEPTORS/TRK
TYROSINE RECEPTORS ARE COMPOSED OF A SINGLE HELIX
TRANSMEMBRANE WITH AN EXTR-CELLULAR LIGAND-
BINDING DOMAIN,A TRANS-MEMBRANE AND AN
INTRACELLULAR DOMAIN THAT HAS TYROSINE KINASE
ACTIVITY.
SIGNAL TRANSDUCTION GENERALLY INVOLVES DIMENSION
OF RECEPTORS, FOLLOWED BY AUTOPHOSPHORLYATION OF
TYROSINE RESIDUES. THE PHOSHOTYROSINE RESIDUE ACTS
AS ACCEPTORS FOR THE SH2 DOMAIN'S OF A VARIETY OF
INTERCELLULAR PROTIENS,THEREBY ALLOWING CONTROL
OF MANY CELL FUNCTIONS.
ENZYME INVOLVED
EXAMPLES OF LIGANDS THAT BIND TO TYROSINE KINASE
ARE-
INSULIN,NERVE GROWTH FACTOR,PLATELET DERIVED GROWTH
CYTOKINES & OTHER GROWTH FACTORS.
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TYROSINE RECEPTORS/TRK
A FEW HORMONE RECEPTORS (ATRIAL NATRIURETIC
FACTOR) HAVE A SIMILAR STRUCTURE AND LINKED
TO GUANYLATE CYCLASE.
CYTOKINE RECEPTORS HAVE AN INTRACELLULAR
DOMAIN THAT BINDS AND ACTIVATES CYTOSOLIC
KINASES WHEN THE RECEPTORS IS OCCUPIED.
THEY ARE INVOLVED IN THE CELL GROWTH AND
DIFFERENTIATION, THEY ALSO ACT INDIRECTLY BY
REGULATING GENE TRANSCRIPTION.
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Tyrosine kinase receptor
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TYROSINE RECEPTORS
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Kinase linked receptors
.
two important pathways are:
-the RAS()→RAF()→MAP kinase→GENE
TRANSCRIPTION pathway which is important for the
cell division, growth and differentiation.
-the JAK(JANUS-KINASE)→STAT(SIGNAL
TRANSDUCERS & ACTIVATORS OF
TRANSCRIPTION)→GENE TRANSCRIPTION
pathway, which is activated by many cytokines which
is important for the synthesis and release of many
inflammatory mediators.
TWO OTHER LESS IMPOTANT PATHWAYS ARERECEPTOR BY DR.MOHAMMED ABDUL
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Cytokine receptors, like receptor tyrosine kinases, have extracellular
and intracellular domains and form dimers. However, after activation
by an appropriate ligand, separate mobile protein tyrosine kinase
molecules (JAK)are activated, resulting in phosphorylation of signal
transducers and activation of transcription (STAT) molecules. STAT
dimers then travel to the nucleus, where they regulate-transcription.
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NUCLEAR RECEPTOR
 LIGANDS INCLUDE STERIOD HORMONES,THYROID
HORMONES,VITAMIN
 D,RETINOIC ACID,LIPID-LOWERING DRUGS.
 RECEPTORS ARE INTRACELLULAR PROTIENS,SO
LIGANDS MUST FIRST ENTER CELLS.
 RECEPTORS CONSIST OF A CONSERVED DNA-
BINDING DOMIAN ATTACHED TO VARIABLE
LIGAND-BINDING AND TRANSCRIPTIONAL
CONTROL DOMAINS.
 DNA-BINDING DOMAIN RECOGNISES
SPECIFICBASE SEQUENCES,THUS PROMOTING OR
REPRESSING PARTICULAR GENES.RECEPTOR BY DR.MOHAMMED ABDUL
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Nuclear receptor
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NUCLEAR RECEPTOR
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PATTERN OF GENES ACTIVATION DEPENDS
ON BOTH CELL TYPE AND NATURE OF
LIGAND,SO EFFECTS ARE HIGHLY DIVERSE.
EFFECTS UCED AS A RESULT OF ALTERED
PROTIEN SYNTHESIS AND THEREFORE ARE
SLOW IN ONSET.
ONE TYPE OF NUCLEAR RECEPTOR IS
RESPONSIBLE FOR THE INCREASED
EXPRESSION OF DRUG-METABOLIZING
ENZYMES.
NUCLEAR RECEPTOR
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NUCLEAR RECEPTOR IN ACTION
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Nuclear receptor in action
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DISEASES ASSOCIATED WITH RECEPTOR ABNORMALITIES
ANY ALTERATION IN THE RECEPTORS EITHER IN
FUNCTION,DENSITY OR DAMAGE CAN CAUSE MANY
CLINICAL ABNORMALITIES/AUTOIMMUNE STATES.
 TESTICULAR FEMINIZATION SYNDROME (LOSS OF ANDROGEN RECEPTORS)
 MYASTHENIA GRAVIS (LOSS OF NICOTINIC CHOLINERGIC RECEPTORS)
 DIABETES MELLITUS (LOSS/DAMAGED INSULIN RECEPTORS)
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NON-RECEPTOR MEDIATED MECHANISMS
SOME DRUGS ACT BY DIFFERENT MECHANISMS WITHOUT THE
PARTICIPATION OF RECEPTORS by—
-ENZYMES:H+/K+ ATPase inhibited by OMEPRAZOLE.
-PHYSICAL & CHEMICAL PROPERTIES: ANTACIDS & EDTA.
-ADSORBENT ACTION: PECTIN & KAOLIN.
-OSMOSIS:DEXTRAN & MAGNESIUM SULFATE.
-ANTI METABOLITES: ANTI PROLIFERATIVE drugs.
-PLACEBO PALLIATIVE THERAPY.
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REFERENCES
• Goodman & Gilman’s-the pharmacological basis of
therapeutics(12th edition).
• Rang & Dale-Textbook of pharmacology(7th edition).
• Principles of Pharmacology(2nd edition)-Sharma &
Sharma.
• Katzung’s-Basic and Clinical Pharmacology(11th
edition).
• Bennet & Brown-Clinical pharmacology(9th edition).
• Tripathi’s textbook of pharmacology.
• Netter’s illustrated pharmacology.
• Internet.
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FOR A
PHARMACOLOGIST…
RAOF

THANK YOURECEPTOR BY DR.MOHAMMED ABDUL
RAOF

Acknowledgements
MY KIDS…
ZAMARUD
ZAINAB
ZAIN
RAOF

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