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What are the 2 mechanisms of intercellular communication?
- 1. Direct Communication through Gap Junctions
- 2. Indirect Communication through Chemical Messengers
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Describe Gap Junctions
- Channels formed between 2 cells
- - Protein channels made of connexin
- - 6 connexins = 1 connexon
- Allow flow of ions
- Direct electrical and metabolic coupling
- Common in smooth and cardiac muscles
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What are the functional classifications of chemical messengers?
- Paracrines
- Autocrines
- Neurotransmitters
- Hormones
- Neurohormones
- Cytokines
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Describe Paracrines
Released by cell, moves to target cell by diffusion, act on neighboring cells
LOCAL
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Give an example of a Paracrine
Histamine
Released with tissue damage and causes dilation of local blood vessels
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Describe Autocrines
Subclass of Paracrines
Act on same cell that releases it/source and target are the same
LOCAL
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Describe Neurotransmitters
Messenger of the nervous system; released into the ECF of synaptic cleft from neurons, diffuses to very close target cell
Also called Synaptic Transmission
LOCAL
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Describe Hormones
Messenger of endocrine system; released from endocrine cells into blood, transported in blood to target cell (cell with specific receptor)
Examples: Insulin, estrogen, thyroxin
DISTANCE
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Describe Neurohormones
Special class of hormone; produced by neurons, secreted into blood via ISF, transported to target cell
Examples: ADH, oxytocin
DISTANCT
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What are the solubility classifications of messengers?
- Lipophobic (hydrophilic)
- Lipophilic (hydrophobic)
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Describe Lipophobic Ligands
- Not lipid soluble (is water soluble)
- Does not easily cross cell membrane, may require pumps/channels
- Receptors on cell membrane
- General action of target response is enzyme activation, and membrane permeability changes
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Describe Lipophilic Ligands
- Lipid soluble (not water soluble)
- Easily crosses cell membrane
- Receptor location intracellular
- General action of target response is via gene activation
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What are the chemical class classifications of messengers?
- Amino Acids
- Amines
- Peptides & Proteins
- Steriods
- Eicosanoids
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Describe Amino Acid Messengers
- Lipophobic
- 4 AA are chemical messengers, all neurotransmitters
- 1. Glutamate
- 2. Aspartate
- 3. Glycine
- 4. GABA
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Describe Amine Messengers
- Lipophobic (except thyroid hormones)
- Derived from AA
- Contains amine group (NH2)
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Give examples of amine messengers
1. Catecholamines - derived from tyrosine, includes Dopamine, Norepinephrine, Epinephrine
2. Thyroid Hormones - derived from two tyrosine AA
3. Histamine - derived from histadine
4. Serotonin - derived from tryptophan
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Describe Peptide & Protein Messengers
- Most abundant ligand
- Lipophobic
- Made of chains of AA
- Peptide ligand < 50 AA
- Protein ligand > 50 AA
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Describe Steroid Ligands
- Lipophilic
- Derived from cholesterol
- All function as hormones
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Describe Eicosanoid Ligands
- Lipophilic
- Derived from arachidonic acid (cell membrane phospholipid)
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What are the methods of synthesis and release in chemical messengers?
- Lipophilic Messengers - Diffusion
- - Released upon synthesis
- - Cannot be stored, synthesized on demand
- Lipophobic - Exocytosis
- - Stored in vesicles prior to release
- - Regulate rate of exocytosis
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Which functional classes are transported via diffusion?
- Paracrines
- Autocrines
- Neurotransmitters
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Which functional classes are transported via blood?
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What affects a messenger's half life?
Whether it is dissolved in the plasma or bound to a carrier protein.
- Dissolved - short HL, ex. insulin (10 min)
- Bound - long HL, ex. cortisol (90 min)
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Define Receptor
Protein with specific binding sites for messengers
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What are properties of receptors?
Specifity to messenger
Often more than one type of receptor for one messenger
One cell may have receptors for diff messengers or diff types of receptors for one messenger
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What affects the magnitude of response?
- # of receptors with messengers bound to them
- Concentration of messenger
- # of receptors on target cell
- Affinity of receptor for messenger
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Define Signal Transduction
Process by which messenger binding to receptor produces response in target cell
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What does Signal Transduction depend on?
Messenger and Receptor Types
- Lipophilic messenger - Receptor inside cell
- Lipophobic messenger - Receptor on plasma membrane
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Describe Lipophilic Messengers
- Bind to receptor in cytoplasm or nucleus
- If cytoplasm, rec/mes complex enters nucleus
- Alters transcription
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Describe Lipophobic Messengers
- Bind to membrane-bound receptors
- Channel-linked Receptors
- Enzyme-linked Receptors
- G Protein-linked Receptors
- "Cascade" of events
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Define Channel-linked Receptors
Receptor that opens/closes ion channels in response to messenger binding
- 1. Fast ligand-gated channels
- 2. Slow ligand-gated channels
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What is the difference between fast and slow ligand-gated channels?
Fast ligand-gated channels - receptor and channel are on the same protein
Slow ligand-gated channels - receptor and channel are on seperate proteins, linked by G Protein, changes in transport of ians through channel causes target response
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Describe Enzyme-linked Receptors
- One protein for receptor and enzyme
- No channels
Examples: Tyrosine kinase, Guanylate cyclase
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Describe G Protein-linked receptors
- G Proteins are regulatory proteins
- G Proteins link ECF messenger to ion channels or amplifier enzymes
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Define First Messenger
Extracellular messenger
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Define Second Messenger
Intracellular messenger
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How are second messengers produced? List the steps.
- First messenger binds to receptor and activates G protein
- G protein activates amplifier enzyme
- Amplifier enzyme activates production of second messenger
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What are the 2 types of G Proteins?
Gs - stimulatory; activates amplifier enzyme
Gi - inhibitory; inhibits amplifier enzyme
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What is the purpose of the second messenger?
Signal amplification
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List types of second messengers
- Cyclic AMP - cAMP (most common)
- Cyclic GMP - cGMP
- Inositol triphosphate - IP3
- Diacetylglucerol - DAG
- Calcium ions
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