Classical receptors

Receptor Examples

Nicotinic ACH receptor

5-hydroxytryptamine type 3 (5-HT3) receptors

GABA type A receptor

5 subunit ligand

2 neurotransmitter binding receptors

Upon binding, channel changes
conformation to allow ions to pass

primarily mediate chloride transport

Rapid response upon binding

onset time is equal

Duration of effect can vary

Ligand Examples

ACH

5-HT

Dopamine

Opioids

7 transmembrane Alpha helicies

Rapid response upon binding

Subfamilies

Rhodopsin

Secretin/glucagon

metabotropic glutamate receptor/Ca sensor

Alpha beta and Gamma subunit

Beta and gamma stay bound

upon binding Alpha subunit converts GDP to GTP

GTP activates effector protien

Alpha subunit may continue affect
effector protein randomly

Beta and Gamma subunits may bind targets

May activate or inhibit effector protien

Sesceptable to desensitization

Occurs through phosphorylation of cytoplasm tail

Caused by excessive activation of GPCR

Clinically, may need to increase dosage over time

Structure

Binding triggers dimerization of receptor

Large extracellular binding site

Intracellular domain

Ligand examples:

Insulin

Growth factors

Cytokines

bacterial lipopolysaccharides

Receptor examples

Receptor tyrosine kinases

Growth factor receptors

Toll like receptors

Serine/Threonine kinase

Transforming growth factor receptor

Cytokine receptors

Associate with Cytosolic tyrosine kinases

Classical receptors

Main topic of lecture

ion channels

Enzymes

Transporters

Drug target exceptions

Drugs target other specific protiens

structural protiens

Signaling protiens

Drugs target nucleic acids

DNA/RNA metabolism

Antisense and siRNA targets

Structure

DNA Recognition and binding domain

Ligand binding domain

C terminal domain

Governs nuclear localization

N terminal domain

Controls interactions with cofactors

Ligand examples

many hormones

Vitamin D

Orphan receptors

No well defined ligand

Example

RXR receptor

Subtopic

Some of the slowest response times

Hours to days

Types of nuclear receptors

Tyoe 1

Found in cytoplasm

Form homodimers on ligand

primarily bind:

Glucocorticoids

Mineralocorticoids

oestrogen, progesterone, androgen

Hybrid

Form obligate heterodimers with RXR

Examples

Thyroid hormone receptor

Vitamin D receptor

Type 2

primarily in nucleus

form homodimers with Retinoid x receptor

common receptor types

Fatty acid receptors

Cholesterol receptors

xenobiotic receptors

Activates drug metabolizing
enzymes such as CYTP3A