Classical Target Drug Receptors

membrane bound

Composition

extracellular domain

cytoplasmic domain

transmembrane domain

4

fast response: milliseconds

selective channels

Cation selective pores

Receptos

5-HT3 receptors

drug target of psychoactive drugs

anion selective pores

mediate chloride transport

Receptors

GABA

other biological ligands

arachadonic acid sensitive receptors

respond to intracellular binding signals

calcium binding receptors

atp recepots

membrane bound

composition

extracellular domain

N-terminal

cytoplasmic domain

C-terminal

transmembrane domain

7

fast response: seconds

GPCR ligands

Dopamine

Opioids

Act on different types of receptors

ACh

5-HT

GPCR Subfamilies

Rhodopsin

largest group

protanoids and cannabinoids

amine neurotransmitters

neuropeptides

purines

ligands bind to helices of EXC hoops

short EXC tail on N-terminal

Secretin/glucagon

peptide hormones

calcitonin

intermediate EC tail

metabotropic Glu Receptor/Ca Sensor

GABAb receptors

small groups

Subtopic

desensitization

downregulation of receptor

phosphorylation

threorine and serine

nonspecific kinases

Protein Kinase A and C

Receptor internalization

endocytosis

membrane bound

Composition

extracellular domain

cytoplasmic domain

transmembrane domain

1

response time: hours

Ligands

Function in controlling:

inflammation

tissue repair

cell cycle progression

apoptosis

immune response

growth factors

cytokines

hormones

types

insulin

bacterial lipopolysaccharides

End Result: activation or inhibition of nuclear transcription factors by:

phosphorylation

suppression or activation of target genes

Kinase Receptors

RTK

growth factor receptors (EGF and NGF)

TLRs

bacterial infection mediate response

Serine/Threonine Kinase

TFG receptor

Cytokine Receptors

no intrinsic kinase activity

associated with cytosolic tyrosine kinases (JAK)

no transmembrane domain

do not reside in membrane

found in cytoplasm or nucleus of cell

thus separate receptor and DNA binding domains

monomeric

function

directly interact with DNA

modulates transcription

response time: hours to days

subfamilies

Class I

found in cytoplasm

form homodimers

primary receptors to steroid hormones

glucocorticoids

mineralocorticoids

estrogen, progesterone, and androgen

Class II

found in nucleus

form heterodimers with RXR (retinoid x receptor)

include receptors for

fatty acids

cholesterol

xenobiotic

Cyt. P3A for metabolization of drugs

Class III

Hybrid class

form obligate heterodimers with RXR

small includes receptors for

Thyroid hormones

Vit. D receptor

Might contain or have a non-genomic target interacting directly with cytosolic proteins