allows binding of
ligand binding
Ligand binding initiates
On binding to dimers
Allows binding to DNA
Ligand binding initiates
Inactive steroid receptors
Subclass
Low affinity
High affinity
connected by flexible hinge
monomeric
HOURS to DAYS
Anion selective pores
Mediates Chloride flux
Conformational change
Cation-selective
Both alpha subunits must bind ACh
Intracellular
Extracellular domain
Transmembrane domain
Conformational change
Conductance between drugs does not vary
Binding of
MILLISECONDS
No integral kinase moieties
Transforming
Toll-like receptors
Receptors for
Further phosphorylation
Conformational intracellular change
SH2 domain
Phosphorylates
Cytokine receptors
Tyrosine-kinase-linked receptors
Single transmembrane helix
HOURS
Endocytosis
complex
binds target effector protien
Upon binding single agonist
grouped into 4 families
diffuse around cytoplasmic surface of cell membrane
Anchored to membrane by lipid residues
SECONDS
Small group
intermediate extracellular tail
receptors for
Short extracellular N-terminal tail
Largest group

Pharmacodynamics Module 1

Classical Receptors

GPCR

Structure

Membrane-localized

7 transmembrane
alpha helices

Intracellular g-protein
coupling domain

Subfamilies

Rhodopsin

Amine NT, NP,
purines, cannabinoids

extracellular helices or
hoops bind ligands

Secretin/glucagon

peptide hormones

ligand binding domain

Metaboropic glutamate

GABA

Calcium sensor

G-proteins

Structure

Alpha, beta, gamma subunits

20 alpha isoforms

some activate, some inhibit

associate with ligand-bound
receptors

Activation

1. GDP --> GTP

2. Release subunits

Alpha subunit switches off
by self-hydrolysis of GTP

Beta and gamma reunite with
dissociated alpha, await recycle

Desensitization

Receptor phosphorylation

Receptor internalization

Kinase-linked

Structure

Membrane-localized

Links extracellular domain to
intracellular kinase domain

Transduction

Intrinsic kinase activity

proteins bound to activated
intracellular domains

Recognizes phopshotyrosine domain

Cytokine binding to extracellular domain

Allows binding of independent
cytoplasmic kinase

Activation of other proteins,
transcription factors

Related receptors

Tyrosine kinases

GFs

Response to
bacterial infection

Serine/threonine kinases

GFR

Cytokine

Associate with cytosolic
tyrosine kinases

Ligand-gated ion channel

Activation

Hyperpolarization or
Depolarization

Ligand or Agonist

Ion passage

Period of opening varies

Structure

Membrane localized

Ion pore

Ligand binding

Pentameric complex

Sequence homology

Examples

Nicotinic ACh receptor

2 ACh binding regions

Activation of channel

Ion passage

Central aqueous
pore

GABA Type A

Binding of GABA to
alpha/beta interface

Psychoactive drug targets

Nuclear

Structure

DNA recognition/binding domain

ligand binding domain

Subfamilies

Class I

Cytoplasmic homodimers

Endocrine ligands

Class II

Intranuclear heterodimers

Lipid ligands

Hybrid

RXR heterodimers

Endocrine

Mechanism

Class I

Heat shock proteins
in cytoplasm

Dissociation from HSP

HRE on target genes

Recruit co-activators/repressors
that effect gene transcription

Class II

heterodimerization with
retinoid X receptor

often causes dissociation
of co-repressor

co-activating protein