This document discusses different types of receptors and their mechanisms of action. It describes four main types of receptors: G-protein coupled receptors (GPCRs), ion channel receptors, transmembrane receptors, and nuclear receptors. For each receptor type, it provides examples and explains their signal transduction pathways. Key points covered include GPCR effector mechanisms through G proteins, second messengers like cAMP and IP3, and downstream effects. The document also discusses various ion channels like voltage-gated and receptor-operated channels, as well as receptors for neurotransmitters and hormones.

1. DR. ARTHI
POST GRADUATE
MD PHARMACOLOGY
RAJAH MUTHIAH MEDICAL COLLEGE

2. .
• CELLULAR MACROMOLECULAR COMPLEX WITH
WHICH ITHE DRUG INTERACTS TO ELICIT A
CELLULAR RESPONSE.
• DRUGS CAN ACT EXTRACELLULAR, CELLULAR AND
INTRACELLULAR.
RECEPTOR
• RECEPTOR - DRUG COMPLEX -EFFECTOR PROTEIN -
SIGNAL TRANSDUCTIONSMECHANISM
• AFFINITY ; INTRINSIC ACTIVITY OR EFFICACY
• AGONIST ; ANTAGONIST
• PARTIAL AGONIST ; INVERSE AGONIST
TERMS

4. TYPES OF RECEPTORS
1) G-PROTEIN COUPLED RECEPTORS (GPCR)
2) ION CHANNEL RECEPTORS - VOC AND ROC.
3) TRANS MEMBRANE RECEPTORS- RECEPTOR TYROSINE KINASES ;
JAK- STAT; SERINE-THREONINE;
TOLL-LIKE; TNF-α
cGMP RECEPTORS
4) NUCLEAR RECEPTORS - CYTOSOLIC AND NUCLEAR

5. G PROTEIN COUPLED
RECEPTORS(METABOTROPIC)
• 7 ALPHA HELICAL PROTEIN WITH
2 DOMAINS
• HETEROTRIMERIC MOLECULE- α,
β, ￥ SUBUNITS TIGHTLY BOUND
TOGETHER WHICH OCCURS IN
RESTING STATE
• EFFECTOR MECHANISMS

6. Effector Mechanism
G-
PROTEIN
cAMP
PHOSPHO
LIPASE-C
ION
CHANNELS

7. GS: ADENYLYL CYCLASE ACTIVATION, Ca
CHANNEL OPENING
Gi: ADENYLYL CYCLASE INHIBITON, K+
CHANNEL OPENING
Go: Ca CHANNEL INHIBITION
Gq: PHOSPHOLIPASE- C ACTIVATION- IP3
AND DAG.
GPCR

8. CYCLIC AMP
• IS A PROTOTYPE SECOND MESSENGER FROM ADENYLYL CYCLASE.
• cAMP INCREASED IN GS AND cAMP DECREASED IN Gi PATHWAYS.
WHEN LIGAND(Adrenaline) BINDS TO GPCR,
↓
GS-α +GTP
↓
ACTIVATES ADENYLYL CYCLASE
↓
CAMP IS FORMED
↓
PHOSPHOKINASE A
PHOSPHOKINASE A - PHOSPHORYLATES AND ALTERS THE FUNCTION OF MANY ENYMES, ION
CHANNELS, TRANSPORTERS, TRANSCRIPTION FACTORS, STRUCTURAL PROTEINS.

10. • β￥ DIMER- CAN REGULATE ION CHANNELS, PI3
KINASE
• cAMP FUNCTIONS:
a) cAMP RESPONSE ELEMENT BINDING PROTEIN
b) CYCLIC NUCLEOTIDE GATED CA2+CHANNEL,
PDES,SEVERAL ABC TRANSPORTERS MRP4 AND MRP5.
c) REGULATES GUANINE NUCLEOTIDE EXCHANGE
FACTORS (EPAC)
• TERMINATION - BY PDES INTRACELLULARLY BY PDE3
AND PDE4. WHEREAS CGMP BY PDE5.

11. PHOSPHOLIPASE C (PLC)
ACTIVATED GTP WITH Gq-α SUBUNIT
↓
PIP2 PHOSPHORYLATION BY PLC
↓
SECOND MESSENGERS IP3 AND DAG
↓
DAG REMAINS IN MEMBRANE
;ACTIVATES PKC ALONG WITH ↓
Ca2+.
IP3 MOBILISES Ca2+ FROM ER→Ca-
CALMODULIN COMPLEX→EFFECTS→MLCK
AND CCPK.

12. PL-C HAS 2 ISOFORMS
PLC-βACTIVATED BY GPCR
PLC-￥ACTIVATED BY TYROSINE
PHOSPHORYLATION

13. ION CHANNELS
ACTIVATED G- PROTEIN OPEN OR INHIBIT Ca OR K CHANNELS
WITHOUT SECOND MESSENGERS.
eg: M2 RECEPTORS IN CARDIAC - ↑ K＋ PERMEABILITY.
OPIODS REDUCE NEURONAL EXCITABILTY- K＋ OPENING
MUSCARINIC M1,M3, M5
M2, M4
Gq
Gi,Go
ADRENERGIC ɑ1
ɑ2
β
Gq
Gi,Go
Gs
DOPAMINE D1
D2
Gs
Gi,Go
SEROTONIN 5HT1
5HT2
Gi,Go
Gq

14. ION CHANNEL RECEPTORS

15. VOC ROC
• MODULATED BY ALTERATIONS IN
VOLTAGE GRADIENT
• 3 STATES: OPEN
CLOSED/BLOCKED
INACTIVATED/REFRACTORY
eg: Na＋ channel; K ＋channel; Ca2＋
channel
• CHANNEL WITH A RECEPTOR
SITE
• ROC HAS 2 STATES - OPEN
CLOSED
eg: nicotinic Ach, Glutamate,
5HT3,GABA & Glycine
ION CHANNELS

16. VOLTAGE GATED CHANNEL:(VOC)
• Na channel - subunits
• P LOOP AND S4 HELIX
• LOCAL ANAESTHETICS,
ANTI-ARRYTHMICS

17. Na+ Channel

18. Ca 2＋ CHANNEL
• WHEN MEMBRANE IS
DEPOLARISED -40mv
• 5 TYPES L , T , N, P & Q
CHANNELS
• L- TYPE CHANNEL ARE
BLOCKED BY CCBs.

19. K ＋ CHANNEL
β
VOC K+
channel
• vascular and
smooth muscle
• opens when
membrane is
depolarised.
Ca2+ activated
K+ channel
• intracellular
ca2+increases , k+
influx-
repolarisation
• 5HT ,Ach ,NE
ATP sensitive
K+ channel
• cardiac muscle ,
beta cells of
pancreas.
• blocked by SUFI-
INSULIN release
by depolarisation.

20. Receptor Gated Channel:(ROC)
• LIGANDS- EXCITATORY NT-
Ach; Glutamate.
• INHIBITORY NT-
Glycine;GABA
• MAJORITY OF SYNAPSES IN
CNS &ANS.
• MEMBERS OF KV FAMILY
• cAMP GATED (HCN)
CHANNEL IN HEART
• CNG CHANNEL FOR VISION
• K ATP SENSITIVE CHANNEL IN
β CELLS OF PANCREAS -
INSULIN RELEASE BY
SULFONYLUREAS &
MEGLITINIDES.
• 5HT3
ANTAGONIST(ONDANSETR
ON) ON AFFERENT VAGAL
NERVES-

21. Insulin release
ATP INCREASE
BLOCKS K+
CHANNELS- WITH
SUBUNITS Kir6.2
and SUR1 WHICH
CAUSES CA2+
MEDIATED
EXOCYTOSIS OF
INSULIN RELEASE
FRON VESICLES.

22. ION CHANNEL-ROC-EXCITATORY
Ach Nicotinic NN receptor
• CNS, GANGLIA AND
NMJ(NM)
• PENTAMERIC 2 ,β,￥,θ
IN NMJ (NM ) whereas
2ɑ,3β in GANGLIA (NN)
• EACH SUBUNIT HAS 4
HELIXES
• EACH ɑ SUBUNIT HAS
Ach BINDING SITE

23. ION CHANNEL-ROC-EXCITATORY
Glutamate Receptor
• THEY ARE 5 IN NUMBER
• 3 IONOTROPHIC- NMDA
AMPA
KAINATE
• AP-4: INHIBITORY AUTO
RECEPTOR
ACPD: Metabotrophic Gq
AMPA & KAINATE- NON
NMDA RECEPTORS.

24. N-methyL-D-asparate(NMDA)
• ROC, PENTAMERIC
• NR1, NR2 SUBUNITS
• HAS 6 BINDING SITES
• HIGH PERMEABILITY TO
Ca 2 ＋AND Na＋

25. MOA Anti epileptic drugs
• 1. Phenytoin, CBZ,
Valproate, lamotrigine,
lacosamide
• 2.Lamotrigine,GAbapen
tin,Pregabalin
• 3.FElbamate
• 4.Phenobaribitone,topir
amate,lamotrigine
• 7.Ethosuximide,
Valproate.

26. GABA
- inhibitory NT in cns.
- CL channel→hyperpolarisation
• GABAA - presynaptic
• IONOTROPIC
• GABAB- GPCR
• Pre & post synaptic
ca2+ inhibition, k+
opening
hyperpolarisation &
cAMP reduces.
• GLYCINE: Pentameric
• similar to GABA -Linked
to Cl －Channel.

27. TRANSMEMBRANE RECEPTORS
a) RECEPTOR TYROSINE
KINASES
• EPIDERMAL GROWTH
FACTOR
• INSULIN RECEPTORS
• PDGF,FGF,VEGF
b)TYROSINE KINASE
associated
• JAK-STAT
• SERINE-THREONINE
KINASES
• ANP RECEPTORS
• TOLL- LIKE RECEPTORS
• cGMP RECEPTORS

28. Receptor Tyrosine Kinase (RTK)
• a)aa

29. JANUS-KINASE -STAT
JAK PHOSPHORYLATES
STAT-SIGNAL
TRANDUCER AND
ACTIVATORS OF
TRANSCRIPTION.
4 JAK AND 6 STAT
eg: PROLACTIN -JAK1,2
AND STAT 5 FOR MILK
PRODUCTION.
GH, INF-￥

30. • SERINE-THREONINE
KINASES AT THE
CYTOPLASMIC DOMAIN
INSTEAD OF RTK.
• eg: TGF-β
• TYPE 1- 7 ISOFORMS
• TYPE 2- 5 FORMS
• SMAD PROTEINS
• INHIBITORY SMADS-6
AND 7.

31. TOLL-LIKE RECEPTORS
• INNATE IMMUNE SYSYTEM-
HAEMPOIETIC CELLS
• INTRACELLULAR DOMAIN IS
TIR DOMAIN
• LIGANDS- LIPIDS,
PEPTIDOGLYCANS,
LIPOPEPTIDES AND
VIRUSES.
• TNF-ɑ: TYPE 1, 2
• TRIMERIZATION- DEATH
DOMAIN is IC domain.

32. cGMP Receptors
• Guanylate cyclase is
transmembrane here
• ligands- ANP, NO
• Intracellular domain - GC
domain
• NO stimulates GC
→cGMP produced.
• EFFECTS: BP↓ , reduces
cardiac hypertrophy &
fibrosis.

33. Nuclear hormone Receptors
• cytosolic- steroids and sex
hormones
• Nuclear -TR, PPAR,
RXR,LXR,FXR, vitamin A & D
Receptors.
• heterodimers. slow & long
lasting process.

34. • Time for Gene Transcription:
• GPCR : Few sec to min
• Ion channels: milli seconds
• Tyrosine kinase :minutes
• nuclear: longer time

35. HISTAMINE
RECEPTORS
H1- Gq
H2-Gs
H3- Gi
H4-Gq/Go

36. SEROTONIN (5HT )RECEPTORS
5HT1
5HT1A,1B,1D,1E,1F
5HT2
2A,2B,2C
5HT3 5HT4, 5HT5A,B
5HT6,5HT7
Gi
↓ cAMP
Gq
↑PL-c
LIGAND GATED ION
CHANNEL
Gs
DOPAMINE RECEPTORS
D1-D5
VASOPRESSIN
RECEPTORS- ADH ACTS
D1- Gs -↑cAMP
D2-Gi -↓ cAMP
V1-Gq- ↑ PLc
V2- Gs- ↑c AMP

37. Regulation of receptors
• Receptor Desensitisation:Receptor mediated
response after initial high level, gradually
diminishes even in continuing presence of agonist.
• Down regulation: Prolonged exposure to high
concentration of agonist causes reduction in
number of receptors available for activation
• Up regulation:Prolonged occupation of receptors
by a antagonist leads to increase in number of
receptors-receptor sensitivity increases
• Denervation Supersensitivity: In Denervated
muscles, proliferation of new dopamine receptors
eg: tardive dyskinesia