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  response.

stronger cell

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 (NH 2 -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 – NH

2 ):

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) diacyl glycerol(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.