receptors and signal transduction

1. Reseptors
&
Signal transduction
1

2. What is Receptors ??
receptor is a chemically reacting area of
the functional macromolecules (proteins)
which is located either on a cell membrane
or intracellular.
Types of cell receptors and signaling mechanisms
3
I-Cytoplasmic or
intracellular receptors: e.g
receptors of steroidal
hormones
(glucocorticoids, sex
hormones).
II- Transmembrane
receptors: Receptors are
located on the cell
membrane e.g : ligand
reseptor , G-Protein-
coupled receptors

3. Types of reseptors
Ligand gated ion channel
G- proteine coupled reseptor
Tyrosine kinase linked reseptor
Intracellular receptors 4

4. (A) Ligand gated ionic channel receptors:
• They are membrane receptors
located on the gate of ionic
channels.
• Binding of ligand to the receptor
will lead to conformational change
in the receptor and change in cell
membrane permeability to ions.
• (A.Ch) + Nicotinic receptors
Na+ influx
depolarization
Milliseconds between binding of the
ligand and cellular response e.g 5

5. B) G. protein-coupled receptors and second
messenger:
They are cell surface receptors which
facilitate binding of guanosine triphosphate
(GTP) to specific proteins located on the
cytoplasmic surface of plasma membrane
known as G-protein which regulates the
activity of membrane enzymes and ion
channels
• The G-protein is a membrane protein
comprising three subunits (α, β, Ɣ)
• G-protein either: -regulate intracellular 2nd
messenger (α-subunits with GTPase activity)
or- control opening of ion channel (β, Ɣ-
subunits)
6

6. B) G. protein-coupled receptors and second
messenger:
• There are different Gα subunits (Gαs -Gαi - Gαq)
i. Adenyl cyclase (A.C) is regulated via Gαs (c-AMP) and Gαi (c-AMP)
ii. Phospholipase C activated via Gαq responsible for generation of IP3
(inositol triphosphate) and DAG (diacylglycerol) to regulate free calcium
concentration.
- Adrenaline + β-receptors,→ Gαs-protein→ ++ A.C → cAMP
concentration
- Adrenaline + α-2 receptors → Gαi-protein → -- A.C. → cAMP
concentration
• Few seconds - minutes between binding of the ligand and cellular
response
7

7. 6
8
β,ɡ

8. (C) Enzyme (Tyrosine kinase)-linked receptors:
9
They are polypeptide receptors consisting of
an extracellular ligand-binding domain (to
which insulin or growth hormone bind). It is
connected to cytoplasmic enzymatic domain
containing tyrosine kinase enzyme. Which
when activated will phosphorylate and
activate:
ii. Activator of
transcription that will
separate from the
receptor to cross the
nuclear membrane and
modulate gene
transcription → Genomic
actions → Hours e.g.
anabolic effect of insulin
and growth hormone.
i. Signal transducer
→ Non-genomic
actions → Seconds –
Minutes e.g.
hypoglycemia of
insulin.

9. 9
10

10. (D) Gene-active intracellular receptors
(DNA linked receptors):
They are cytosolic or nuclear receptors that modulate the
transcription of genes in the nucleus leading to change in protein
synthesis.
 • e.g. Lipid soluble ligands (steroid hormones, thyroxine , vit. D) +
Intracellular receptors → DNA transcription → mRNA → change in
protein synthesis.
 • Delayed long-lasting effect (hours between binding of the ligand
and cellular response).
 e.g : steroid hormones
11

11. 12

13. Biological effects of drug
reseptor binding
02
14
Agonist Antagonist Partial agonist Inverse
agonist

14. 16

15. The drug to which the
receptor has an affinity
for binding with it and
produces intrinsic
activity and response.
a-The receptor agonist
17

16. b-The receptor antagonist
(competitive and noncompetitive)
The drug to which the receptor
has affinity but lacks intrinsic
activity. The receptor
antagonist is the drug that
blocks the receptor and does
not produce a response but
prevents other drugs
(agonists) from interacting
with the receptor. 18

17. Types of Antagonist
19

18. Reversible ,ylbisrever dniB :
eht fo msilobatem yb dne tceffe
antagonist e.g. Nicotine large
dose, suxamethonium
Irreversible ,yltnelavoc dniB :
wen fo sisehtnyser yb dne tceffe
receptor e.g. organophosphates,
phenoxybenzamine
Competitive antagonist
20

19. c- partial agonist:
Drugs to which the
receptor has an adequate
affinity and produce low
intrinsic activity. In
absence of the full agonist,
it acts as an agonist and
produces only a small
maximum effect. In
presence of a full agonist, it 21
Ful agonist
Partial agonist

20. d-Inverse agonist:
stimulates the receptor but
produces effects opposite to
those obtained by the
agonist. For example, beta-
carbolines stimulate the
same receptors
(benzodiazepine receptors)
but produce excitation &
convulsions instead of 22

21. Other types of antagonist
Physical :
Positive
"protamine" +
Negative
"Heparine"
Chemica :
Basic
"gentamicine"+
acid"carpinciline"
Intetaction
Physiological
:
Adrinaline = VC
Histamine = VD

22. . . . Other types of antagonist
Pharmacokinetic
s
Absorption
Antacids ..
prevent
absorbtion of
IRON
Metabolism
Rifambin
catalize
mmmetabolis
mof
Contraseptivepill
s
Excretion
NaHCo3 "‫"فوار‬
catalize
Excretion of
Asprin
distribution
Some drugs
prevents
distribution of
another one to
the Brain

23. Chronic use of drug
03
14
UPREGULATION. DOWN-

24. a-Receptor down-regulation
Decreased receptor reactivity
(desensitization) to the agonist
that leads to a reduction of the
drug response (drug tolerance).
Mechanisms of down-
regulation:
Reduction of the receptor
number or decrease of the
sensitivity of the receptors 24

25. Causes of down-regulation:-
1-Prolonged continuous stimulation of
receptors by agonists. The sensitivity of the
receptor returns to its normal level (reversible)
after a period of discontinuation of the agonist.
2-Diseases:
- .; continuous hyperglycemia
reduces the number of insulin receptors or
decrease their sensitivity to insulin.
25

26. b-Receptor upregulation
Increased receptor reactivity
(supersensitivity) to the agonist
leads to exaggerated responses.
Mechanism of upregulation:
Increase of the number of
receptors or increase of the
receptor sensitivity to the
agonist.
26

27. Causes of upregulation:
1-Prolonged use of the antagonist with the absence
of the agonist.
2-Certain drugs, e.g. , ,
…etc. lead to the supersensitivity of
receptors to .
3-Some diseases e.g. . Excess
thyroxine leads to supersensitivity of beta receptors
to catecholamines
-Drugs associated with this phenomenon should be
gradually withdrawn to avoid severe withdrawal 27

28. Thank you