Download Chemical Messengers - IUST Dentistry

Chemical Messengers
Mechanism of intracellular
communication
• Direct: Cells are physically linked by gap
junctions (few instances).
• Indirect: Cells communicate through chemical
messengers (most instances).
Gap junctions
• Gap Junctions are formed by plasma
membrane proteins, (called connexins) that
form the structures, (called connexons) that
form channels for ions and small molecules.
• The movement of small molecules through
gap junctions metabolically couples the cells
and causes cells of organs to act as a unit.
Chemical messengers
• Ligands (from secretory cell) are secreted in
the interstitial fluid  target cells respond by
receptors that bind the messenger  signal
transduction.
• More receptors + messengers  stronger cell
response.
Functional classification
1) Paracrines
• Paracrines: communicate with neighboring
cells.
• Some paracrines: Growth factors – Clotting
factors – cytokines.
• Ex: Histamine: is secreted by mast cells
scattered throughout the body during allergic
reaction or response to Bacterial Infection 
Inflammation.
Inflammation
• Redness: Increase of blood flow.
• Swelling: leakage of fluid out of blood vessels
into the affected tissues.
2) Autocrines
• Act on the same cell. (secretory cell = target
cell).
• Often function as paracrines and regulate
their own secretion.
3) Neurotransmitters
• Neurotransmitters are released from neurons,
specialized portion called axon terminal. Very close to
the target cell.
• Synapse: is the junction between two cells.
• Synaptic signaling: is the communication by
neurotransmitters.
• Presynaptic neuron: is the cell releasing the
neurotransmitter.
• Postsynaptic neuron: is the target cell ( another
neuron, gland cell, muscle cell).
• Ex: Acetycholine : causes contraction of skeletal
muscles.
4) Hormones
• Hormones: are released from endocrine
glands and diffuse into the blood, then travel
to their target cells which possess receptors
specific for the hormones.
• Ex: Insulin is secreted by pancreas and
regulates energy metabolism.
Neurohormones
• Neurohormones, are released by a special
class of neurons (neurosecretory cells) and
diffuse into the blood.
• Ex. Vasopressin = (ADH = antidiuretic
hormone) is synthesized in the hypothalamus
(brain in the posterior pituitary gland) and
travels to target cells in the kidneys to regulate
excretion of urine.
Note !
• One chemical messenger may fit more than
one functional class.
• Ex: Serotonin is a neurotransmitter when
released from neurons. But it is a paracrine
when released from platelets.
Chemical Classification
• Chemical structure determines:
(Synthesis. Release. Transport. Signal transduction).
• Messengers dissolving in water = lipophobic =
hydrophilic = don't cross the plasma membrane.
• Messengers which cross the lipid bilayer in the
plasma membrane = (lipophilic = lipid-soluble) =
hydrophobic.
Chemical Classification
1) Amino Acids:
2) Amines: lipohobic except  thyroid
hormones are lipophilic + receptors in the
nucleus of target cells.
3) Peptides / Proteins.
4) Steroids.
5) Eicosanoids.
6) Others: Acetylcoline + Nitric Oxide.
1) Amino acids
• Amino Acids (NH2-RCOOH): are the
Neurotransmitters in the brain and spinal cord.
• Glutamate, Aspartate and Glycine: are alpha Aa
used in protein synthesis.
• Gamma – aminobutyric acid (GABA).
• Amino acids are lipophobic.
2) Amines
• Amines ( R – NH2 ):
1) Catecholamines: contain catechol group = a six-carbon ring,
derived from tyrosine Aa. and include:
• Dopamine – norepinephrine: (function as neurotransmitters)
• epinephrine: (functions as a hormone).
2) Serotonin = neurotransmitter derived from tryptophan.
3) Thyroid hormones = neurotransmitter derived from tyrosine.
4) Paracrine histamine = neurotransmitter derived from
histidine.
5) Amines are lipophobic: except Thyroid hormones (Amines but
lipophilic)
3) Peptides / Proteines
•
•
•
•
Peptide (protein) messengers: 2 ~ > 100 Aa.
(peptide =< 50 Aa)
(protein => 50 Aa).
They are lipophobic.
4) Steroid messengers
• Derived from cholesterol.
• Lipophilic / insoluble in water / cross plasma
membrane.
• Steroids can not be stored but synthesized on
demand and released immediately.
5) Eicosanoids
• Eicosanoids are :
-Prostaglandins
-Leukotrienes
-Thromboxanes
• Eicosanoids are lipophilic.
Transport of messengers
• Simple diffusion to reach the near target cells.
• Dissolution in blood to reach far place.
• Carrier proteins for hydrophobic molecules.
Carrier proteins
• Some carriers are specific for a particular
hormone.
Ex: corticosteroid-binding globulin which
transport the hormone ;cortisol.
• Other carriers transport many hormones.
Ex: albumine.
• Hormones with carriers have longer half-life
than dissoluble forms.
Signal Transduction Mechanism
by intracellular receptors
• The complex hormone-receptor binds certain
region of DNA called the Hormone response
element (HRE), which is the beginning of a
specific gene.
• Then, the gene is activated or deactivated.
• If activated, mRNA is transcribed and moves
to cytosol.
• mRNA is translated to proteins by ribosomes.
Signal Transduction Mechanism
by Membrane-Bound Receptors
• The receptors for lipophobic mesengers fall
into three categories:
1) Channel-linked receptors.
2) Enzyme-linked receptors.
3) G-protein receptors.
Channel-Linked Receptors
• They are specific for some ions and regulated
between open and closed states.
• They fall into 2 categories:
1) Fast channels, in which the receptor and the
channel are the same protein.
2) Slow channels, the receptor and the channel
are separate proteins but coupled by a third
protein called, G protein.
Calcium Ion-channel
• Calcium channels when open, calcium enters
the cell as second messenger and binds a
protein called calmodulin.
• The complex activates a protein kinase which
phosphorylates other proteins to work.
Enzyme-Liked Receptors
• They are trans-membrane proteins with the
receptor side facing the interstitial fluid and
the enzyme side facing the cytosol.
• Most of them are tyrosine kinases, which
phosphorylate the amino acid tyrosine in
certain locations in target proteins.
G protein-Linked Receptors
• They activate specific membrane proteins
called G protein.
• Activated G proteins can activate or inhibit
intracellular proteins.
• Many of them activate the formation of
second messengers:1) cAMP mainly, 2) cGMP,
3) inositol triphosphate(IP3), 4) diacylglycerol(DAG), and 5) calcium.
Nervous system and Endocrine system
• Responses triggered by neural signals are
generally fast and brief.
• Responses by Endocrine system are slow and
long lasting.
• Neurons send signals to specific target cells
which are connected to by synapses.
• Endocrine system broadcasts signals to target
cells throughout the body.