APK 2105C Lecture Notes - Lecture 35: Thromboxane, Aspirin, Phenoxybenzamine

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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 distancetarget 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 solubledo not like lipids
Cannot diffuse through plasma membrane
o Steroids and eicosanoids are lipid structures and are lipophilicthey 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 neuronsnot from gotten food
Synthesized in the cytosol
Can do this because they’re water soluble
Packaged into vesiclesstored 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 hormonesreceptors are on the nucleus
o Hydrophilic
Except thyroid hormoneshydrophobic
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 hormonesall 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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