APK 2105C Lecture Notes - Lecture 35: Thromboxane, Aspirin, Phenoxybenzamine
Chemical Messengers All Lectures
Chapter 5, Lecture 1
Chemical Messengers
• Mechanisms of intercellular communication
o Only a few mechanisms for all cells to communicate with each other
▪ Direct communication between cells
• Gap junctions = transmembrane proteins that fuse together to
form a tunnel between cells
• Electrical coupling
• Metabolic coupling
• Relatively uncommon
▪ Communication via chemical messengers
• Ligand = chemical messenger molecule which binds proteins
reversibly
• Much more common than direct communication
• Some cell secretes chemical messenger (ex: hormones,
neurotransmitters, etc.)
• Transported to another cell to bind with transmembrane receptor
protein
• Results in signal transduction (something happens in target cell as
result)
• Functional classes of chemical messengers
o Paracrines = reach target cells via simple diffusion
▪ Only have to diffuse a short distance—target cell is
nearby
o Autocrines = act on the cell that secreted them
▪ Subclass of paracrines
o Neurotransmitters = chemical messengers released from
neurotransmitters (axons)
▪ Neurotransmitter is exocytosed and diffuses to
target cell
▪ Synapse = space between neuron and target cell
▪ Synaptic signaling
▪ Synapse-specific = neurotransmitters affect certain
cells
▪ Ach → muscle cells
• Causes contraction of skeletal muscle cells
o Hormones
▪ Typically secreted by endocrine cells (sometimes
neurons)
▪ Flow long distance through blood
▪ Get delivered to all cells, but only cells with
receptors will respond to the hormone
• Clinical correlation = histamine
o Mast cells secrete histamine
▪ Histamine is a paracrine
▪ Secreted right into the cells that are affected
o Histamine is part of the inflammation response
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▪ Increases blood flow to the area
▪ Causes capillaries to become more leaky
▪ Cause there to be swelling (and pain, heat associated with swelling)
o Antihistamines block the receptors that histamines bind to
▪ Side effects of antihistamines result because they block ALL histamine
receptors
• Drowsiness = H1 receptor blockade in neurons responsible for
alertness
• Classes of chemical messengers
o Molecule’s chemical structure determines its mechanisms of synthesis, release,
transport, and signal transduction
o Hydrophilic = lipophobic = water soluble—do not like lipids
▪ Cannot diffuse through plasma membrane
o Steroids and eicosanoids are lipid structures and are lipophilic—they can go
through plasma membrane
▪ Why their receptors are on the inside the cell
Class
Chemical Property
Location of Receptors
on Target Cell
Functional
Classification
Amino acids
Lipophobic
Plasma membrane
Neurotransmitters
Amines
Lipophobic
Plasma membrane
Paracrines,
neurotransmitters,
hormones
Peptides/proteins
Lipophobic
Plasma membrane
Paracrines,
neurotransmitters,
hormones
Steroids
Lipophilic
Cytosol
Hormones
Eicosanoids
Lipophilic
Cytosol
Paracrines
• Amino acid messengers
o 4 amino acids function as neurotransmitters in the CNS (not found outside of
CNS)
▪ Used in protein synthesis (alpha-amino acids)
• Glutamate
• Aspartate
• Glycine
▪ GABA (gamma-aminobutyric acid)
o Hydrophilic
o Receptors located on the plasma membrane
o Synthesis and release
▪ Synthesized within neurons—not from gotten food
▪ Synthesized in the cytosol
• Can do this because they’re water soluble
▪ Packaged into vesicles—stored there until exocytosed
• Can do this because they’re not lipid soluble
• Amine messengers
o All posses an amine group (--NH2)
o Catecholamines
▪ Dopamine = primary acts as a neurotransmitter
▪ Norepinephrine = primarily acts as a neurotransmitter
▪ Epinephrine = primarily acts as a hormone
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▪ Derived from tyrosine (initial precursor AA) and is exposed to enzymes
that turn it into the catecholamines
• Enzymes present will determine where the cascade stops and
what is actually secreted
o Serotonic = neurotransmitter
o Histamine = paracrine (acts locally)
o Thyroid hormones = only amine that is lipophilic (hydrophobic)
▪ Receptor is located on the cell nucleus (can go through plasma
membrane to get there)
o Receptors are located on the plasma membrane
▪ Except thyroid hormones—receptors are on the nucleus
o Hydrophilic
▪ Except thyroid hormones—hydrophobic
o Synthesis and release
▪ Derived from AAs
• To determine which amine messenger gets made
o Need to know which AAs are present in the cell
o Need to know which enzymes are present in the cell
▪ Except thyroid hormones—all are synthesized in cytosol
▪ Packaged into vesicles until exocytoses
Chapter 5, Lecture 2
Chemical Messengers
• Classes of chemical messengers
Class
Chemical Property
Location of Receptors
on Target Cell
Functional
Classification
Amino acids
Lipophobic
Plasma membrane
Neurotransmitters
Amines
Lipophobic
Plasma membrane
Paracrines,
neurotransmitters,
hormones
Peptides/proteins
Lipophobic
Plasma membrane
Paracrines,
neurotransmitters,
hormones
Steroids
Lipophilic
Cytosol
Hormones
Eicosanoids
Lipophilic
Cytosol
Paracrines
• Peptide/protein messengers
o Most chemical messengers are polypeptides
▪ Peptide = < 50 AAs
▪ Protein = > 50 AAs
o Hydrophilic = water soluble, not fat soluble
o Receptors located on the plasma membrane (not fat soluble)
o Synthesis and release
▪ Synthesis is same as other proteins (transcription and translation)
▪ Release = proteolytic enzymes in the
golgi or vesicles create the final
product
• mRNA goes into rough ER
• Travels in lumen of rough ER
as prepropeptide
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