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• Signal transduction mediates how cells respond tostimuli.

• Most stimuli impinge from the outside and interactwith the cell membrane.

• “Signalling molecules“ (eg hormones) bind to

receptor proteins in the cell membrane causing a

response. For example, neurotransmitters allownerve cells to communicate across synapses by

interacting with post-synaptic receptors and opening

ion channels (response).

Stimuli

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Stimuli

Types of Signalling Molecules

• Endocrine signals are hormones produced by

endocrine cells, which travel through the blood to

reach all parts of the body.

• Paracrine signals target only cells in the vicinity

of the emitting cell. Neurotransmitters representan example.

• Autocrine signals affect only cells that are of the

same cell type as the emitting cell. An example

for autocrine signals is found in immune cells.

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Types of signals: Hormones

• Most of the molecules that enable signalling

between the cells or tissues within humans

are known as "hormones."

• There are two classes of hormone receptors,

“transmembrane receptors" and

intracellular or “nuclear" receptors.

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Types of signals: Hormones

• Hormone-initiated signal transduction takes thefollowing steps:

 Biosynthesis of a hormone.

Storage and  secretion of the hormone.

Transport of the hormone to the target cell.

 Recognition by the hormone receptor protein

 Relay and  amplification of the signal that leads to

defined biochemical reactions within the target cell.

 Removal of the hormone.

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Structure and Function

Receptors

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• Transmembrane receptors allow communication across

the cell membrane

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• Transmembrane receptors are proteins that span thethickness of the plasma membrane of the cell.

• One end of the receptor is outside (extracellular 

domain) and one end is inside (intracellular domain)

the cell.

Transmembrane receptors

extracellular

intracellular

transmembrane

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• “Receptors ” are macromolecular proteins that

participate in intracellular communication via

chemical signals, such as hormones

• Upon recognition of an appropriate chemicalsignalling molecule (ligand ), receptor proteins

transmit the signal into a biochemical change in the

target cell.

• Receptors bind drugs and initiates the drugs’effects.

Definition of  RECEPTOR:

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Common Features of Receptors

• Receptors are proteins, often glycoproteins or

lipoproteins

• They have one or more binding sites

• Binding of endogenous ligand (eg hormone)activates the receptor by inducing a

conformational change

• One or more signals may be generated

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Common Features of Receptors

• Receptors must have properties of recognition and

transduction

• The magnitude of the transmembrane signal

transduction depends on the fraction of total

membrane receptors occupied by the ligand

• Receptors are saturable because of finite number

of receptors

• Receptors can be up-regulated or down-regulated

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Actions of Drugs on Receptors

• Drugs are receptor modulators and do not confer

new properties on cells and tissues

• Drugs can enhance, diminish or block the generation,

transmission or receipt of a ligand-generated

signal by several mechanisms

• The action of a drug is classified according to whether

it produces (agonist) or diminishes (antagonist)

the signal

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• Drugs can use many sites on the receptor:

1) Agonists and antagonists compete withendogenous transmitters for binding sites

2) Allosteric agonists or antagonists enhance orblock the signal by binding to allosteric sites

that influence signal transmission

3) Other drugs can block signal transduction within

the membrane or at intracellular signal reception

points

Actions of Drugs on Receptors

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Actions of Drugs on Receptors

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• The important value for the strength of the

signal relayed by the receptor is the concentration

of the hormone-receptor complex

• This is defined by the affinity of the hormone

for the receptor, the concentration of the hormoneand the concentration of the receptor.

Hormone/Drug recognition by

transmembrane receptors

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• The equivalent between receptor-bound and

free hormone equals[H] + [R] <-> [HR], with

[R]=receptor; [H]=free hormone; [HR]=receptor-

bound hormone

Hormone recognition by

transmembrane receptors

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• The recognition of a drug or hormone by a receptor

uses non-covalent mechanisms, such as hydrogen

bonds, electrostatic forces, hydrophobic and Van derWaals forces.

Hormone recognition by

transmembrane receptors

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Hormone recognition by

transmembrane receptors

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Most drug-receptor interactions

-reversible

-weak chemical bonds

Irreversible drug-receptor interactions

-not common

-strong chemical bonds (covalent)

-e.g. aspirin, anti-tumour drugs

-usually undesirable

-reversal of effects/toxicity

-mutagenicity/carcinogenicity

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• Ligand-Gated Ion Channels:

eg acetylcholine and GABA-A receptors

• Tyrosine Kinase-Linked Receptors:

eg insulin receptor

• G-Protein Coupled Receptors:

eg beta-adrenergic receptor

• Ligand-Activated Transcription Factors

(nuclear):

eg thyroid and steroid hormone receptors

Major Classes of Receptors