 Release of ligand

 Binding of ligand to
receptors
 Signal transmission to
cytoplasmic portion
 Transmission of signal to
nearby enzyme
 Production of second
messenger
 Activation of signaling
proteins
 Cellular response
 Termination of cell
signaling
Enzyme activation

Change in ion permeability

Activation of nucleic acid synthesis

Change in cytoskeletal organization

• change conformation by adding
or removing phosphate groups
• actions:
– activate or inactivate enzymes
– amplify or reduce protein
interaction
– protein transport
– signal to initiate protein
degradation
Feature Hydrophilic Hydrophobic

Storage Intracellular vesicles Synthesized on demand

Mode of secretion Exocytosis Diffusion across membrane

Means of transport Dissolved in extracellular Short distances: dissolved in

ECF
Long distances: bound to
carrier proteins
Receptor Transmembrane Intracellular or
transmemembrane
effect Rapid Slower or rapid
Peptides/proteins
Amines
Steroids
Lipids
Purines
Gases

“Structures of messengers affects signal

mechanism”
• Hydrophilic
• Synthesized in rER (preprohormone)
• Stored in vesicles (prohormone)
• Exocytosed
• Bind to transmembrane receptors trigerring
signal transduction
• Rapid effect on cell
• Contain amine group (-NH2)
• most are hydrophilic
• thyroid hormone hydrophobic
• True hormones, neurotransmitters, or both
• Ex. Acetylcholine, histamine, dopamine,
epineohrine
• Hydrophobic
• Synthesized in sER or
mitochondria
• Synthesized on demand
• Slow effect on target cell
(gene transcription)
• Cortisol
– rapid,non-genomic effect
• Derived from cholesterol
• Three classes:
– Mineralocorticoids
• Electrolyte balance
• Regulate Na uptake in kidney
• Ex. aldosterone
– Glucocorticoids
• Stress hormone
• Ex. cortisone
– Reproductive hormones
• Regulate sex-specific characteristics
• Ex. testosterone
• Adenosine Monophosphate (AMP),
guanine nucleotides

• Controls activity of other signaling

molecules (neuromodulators)
Nitric oxide
Acts as paracrine and
neurotransmitter
Produced by nitric oxide
synthase (NOS) that adds
O2 to arginine
Short half life (2-30
seconds)
Vasodilator (relaxes
smooth muscles on blood
vessels)
• Sildenafil (Viagra)
– NO activates guanylate cyclase producing
cGMP
– cGMP is quickly removed by
phosphodiesterases (PDE)
– Sildenafil blocks PDE5 found in smooth
muscles of blood vessels in the penis
• Results to continued vasodilation and
continuous blood flow
Intracellular
Bind to hydrophobic ligands
Ligand-gated ion channels
Leads to changes in membrane potential
Receptor-enzymes
Leads to changes in intracellular enzyme activity
G-protein-coupled
Activation membrane-bound G-protein
Leads to changes in cell activities
Gene transcription
Intracellular
Change in concentration brought by L-R complex
Amplifies the signal from the first messenger
Examples:
cAMP, cGMP
Ca2+
Phosphoinositides
Inositoltriphosphate
Diacylglycerol
• Remains in the membrame after breakdown
of PLCβ
• Activates protein kinase C (PKC)
– Phosporylates serine and threonine residues of a
broad range of target proteins

“tumors injected to mice become malignant due to

overexpression of PKC”
• Hydrophilic sugar phosphate
• Diffuses rapidly thru the membrane
• Receptor found on sER releases Ca+ upon
binding
• Ca+ binds to target
molecule