Chapter 5 Vert Phys Students)
76
Chapter 5 Chemical Messengers Dr. LeeShawn D. Thomas, M.S., Ph.D. [email protected] Human Physiology
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Transcript of Chapter 5 Vert Phys Students)
Dr. L.D. Thomas, M.S., Ph.D.
Human Physiology Notes
*** Read the Book ***
Born in Quincy, FL.Graduated from FAMU B.S. Biology
Howard University Medical School M.D.
Graduated #1 in his medical class.
Trained by Dr. Charles Drew
First black to be the President of the American Cancer Society.
First black to be PresidentOf Surgical Oncology.
First black to be President of College of Surgeons.
First afro-american to perform surgery at the University of Florida.
Appointed chair of the Cancer panel by President George Bush, Sr.
Taught and trained 5000 medical students!
“With a good education and HARD WORK, combined
with HONESTY and INTEGRITY, THERE ARE
NO BOUNDARIES!”
Dr. LaSalle Leffall, Jr. M.D.
“What is the hardest task in the world?
TO THINK!”
Ralph Waldo Emerson
“Thinking means connecting things, and stops if they can not be
connected!”Gilbert Keith Chesterton
• 10 trillion cells
• Cells have to communicate to carry out coordinated events.
Direct Communication Through Gap Jx’s
• ___________ – channels that allow ions and small mol’s pass from one cell to another. Made of units called connexins connexons.
– Heart muscle contraction (________signals).– Smooth muscle contraction (Intestine & Blood
vessels).– Carry nutrient in bone cells.– Glands.
Intercellular Communication
Figure 5.1a
• __________________ – when a cell produces (secretes) chem messengers called ______ into the interstitial tissues and it binds (typically reversibly) to a ________ (protein) on a target cell causes response by a target cell.
• As the # of receptors ___; the response .
Indirect communication Through Chem Messengers
Intercellular Communication
Figure 5.1b
• Chem mess’s are based on their f(x) and chem structure.
• Functional Classification of chem mess’s4 main categories Paracrine _________ Neurotransmitter _________
Chemical Messengers
• Paracrine – when a cell secretes a chem signal in the ECF and it binds to a neighboring target cell by simple _________.
• i.e Growth factor (prolif & differentiation);• i.e. Clotting factors (clot blood).• i.e. __________ (commun in Immune sys)• i.e Histamine – released by ______ cells &
causes allergic rx’s & ____________.
Inflamattion redness and ______ blood flow
fluids leak out of _________
into tissue (swelling)
ICE & Temp
block
decrease
InterleukinsInterferons
______, ____PDGF
Heat & Ice Treatment• R.I.C.E.• R = Rest, • I = Ice, • C = Compress • E = Elevate.• Heat – causes ___________.• Ice – causes _________.
Dr. George Rieveschl, Ph.D.• Ph.D. in Chemistry and an
Engineer.• Professor of Chemistry @
U. of Cinn.• He Discovered and
Patented Benadryl.• Pfizer bought the rights to
Benadryl in 1946.• In 1946 he received 5% of
profits ($6 million a year).• 1980’s Pfizer begin making
$180 million a year from the drug.
Tumor
Capillary
Avastin
“Targeted Therapy”
Velociximab
NormalBlocking a protein
Messenger Classification by Function
Figure 5.2a
• Autocrine – a cell secretes a signal and has a receptor to respond to the ______ _______that it secreted.
• Neurotransmitter – chem’s released into the interstitial tissue from the axon terminal of a neuron.– ___________ – jx b/w two cells and comm occurs via
neurotransmitters.
– __________ _neuron – releases the neurotransmitter into the synapse.
– ___________ neuron – neurotransmitter bind to the receptor on the target cell (Neuron, Gland or Muscle cell.
Messenger Classification by Function
Figure 5.2b
Messenger Classification by Function
Figure 5.2c
• Hormones – chem released from endocrine glands into ______________ ________ into bloodstream binds target cell.– i.e. Insulin secreted by pancreas
• Neurohormones – special class of hormones released by a special class of neurons called neurosecretory cells.
• i.e. __________ or ADH (anti-diuretic hormone) syn by neurosecretory cells in the ___________ but released in _______ ________. Regulate _______ and urine volume.
• i.e. Serotonin __________ in the brain. paracrine for ________.
Messenger Classification by Function
Figure 5.2d
Chemical Classification of Messengers• Lipophilic (__________) – are lipid soluble and
crosses the mem readily (H2O insoluble).
• Lipophobic (_________) – H2O soluble and do not cross the cell mem.
• 5 Major classes of Chem mess’s _______ ______ Amines ________/Proteins Steroids ____________
Amino acids • 4 amino acids are called neurotransmitters b/c they
f(x) in the brain and spinal cord. _________ Aspartate _________ Gamma – aminobutric acid (GABA).
Amine Messengers• Derived from amino acids NH2
• Include a group of compounds called catecholamine (catechol group) made from _________.
Part of 20 Amino acids
___________ Norepinephrine
(Noradrenaline) Epinephrine
(Adrenline)
Serotonin - __________ Thyroid hormone - tyrosine Histamine - ___________
Catecholamines(Derived from Tyrosine)
Peptides/Protein Mess’s• Most chem mess’s are polypeptides.• Peptides < less than 50 amino acids; • Polypeptide > 50 amino acids.
Steroids• Derived from _____________.• All steroid f(x) as _________.• _________ & Lipophilic properties.
L-Dihydroxyphenylalanine(L-dopa)
Tyrosine
Tyrosineb-hydroxylase
Catecholgroup
Dopadecarboxylase
Dopamine
Norepinephrine
PhenylethanolamineN-methyl transferase (PNMT)
Epinephrine
Dopamineb-hydroxylase
NH2C
COOH
H
HO
OH
NH2HO CH2
CH2
CH2
OH
NH2CH2
OH
HO CH
OH
NHCH2 CH3
OH
HO CH
OH
NH2C
COOH
H
HO CH2
• Synthesis & Release of Chem Mess’s
• The 4 a.a’s that f(x) as neurotransmitters must be synthesized in the neuron.
Glucose 3-Phosphoglycerate
__________ Aspartate ________
GABA
Steroids • Catalyzed by enz’s in ________
and mito• All steroids can cross the cell
mem as soon as its made and its released.
Mifepristone (RU486) Blocks ___________ from binding to its receptors.
_______ & ______ ______to displace the embryo.
EicosanoidsAre derivatives of
arachidonic acid from membrane phospholipids.
Made on demand and released immediately b/c
they are lipophilic.
COX-1 (norm)
(Inflamm)(Inflamm)(blood clot)(blood clot)
AspirinBlocks Inflam
Blocks _________
Dose of a drug has Diff effects
85mg - inhibit clots350 - inhibit pain
“VIOXX”Chronic Pain &
Inflamm
______ (tiss dam)
( infect)
Transport of Mess’s
• Paracrine• Autocrine• Neurotransmitters
Utilizes diffusion
• Hormones Use bloodstream Dissolved _______ Protein
A) Corticosteroid – binding globulinB) _________ – non specific
• < 1% hormone in dissolved in plasma
• H – Pr H + Pr
• H-amt of free proteinPr-carrier protein;
• Half Life – time it takes ½ the hormone in blood to degraded.
• _______(degraded) _______ (excrete).
• Soluble in H2O (_____ half life).
• Soluble in Lipid (_____ half life); protected by ________ protein.
Signal Transduction• Chem mess’s transmit their signal by binding to
target cells. ________ ________ ________
Properties of Receptors• Receptors have specificity for the mess (class).
• _________– is the strength of binding b/w a mess and receptor.
Figure 5.8
• A single mess’s can bind to more than one ________ and these mess’s receptor have diff ________ for the messenger.
• i.e. norepinip & epinep can bind to the adrenergic receptor. 1, 2, b1, b2, b3
• Single cells can have recept’s for more than one type of mess
• i.e. skeletal muscle have recept’s for both neurotransmitters
___________ __________
Muscle Contraction Glucose uptake
• Relationship b/w recept binding & magnitude of the target cell response.
Depends on 3 factors Mess conc (M) # of _________ (R) __________ of the recept for the mess
• Response of a cell __ as the conc of the mess __
M + R M – R Response•
• Up-regulation - in the # of _________compared to normal conditions. (____ mess’s conc)
• Down-regulation - in the # of recept’s when mess’s conc is higher than normal (prolonged time).
Receptor Agonists & Antagonists• Agonist – ligands that bind to receptor and
________ biological response.
• Antagonist – ligands that bind to a receptor but do __________ a response (competes for binding site). chance of agonist binding
SignalTransductionMechanisms
Rough endoplasmic reticulum
Polypeptide
Golgi apparatus
Prepropeptide Propeptide
Cleavedamino acids
Prepropeptide
Propeptide
Smooth endoplasmicreticulum
Transportvesicle
Cleaved aminoacids
Cleavedamino acids
mRNA
Propeptide Peptide
Secretoryvesicle
Peptide
Cleavedamino acids
(a) Peptide synthesis
Propeptide
1
2 34
56
Peptide and Proteins
Extracellular fluid
Target cell
mRNA
Nuclear envelope
Nuclear pore
Ribosome
Proteins
Hormone-receptorcomplex
Hormoneresponseelement(HRE)
Nuclearreceptor
Nucleus
DNA
mRNA
Lipophilic messenger
Diffusion
Cytoplasmicreceptor
1a
1b
2
3
4
5
Intracellular Mediated Response
Channel-Linked Receptors
Enzyme-Linked Receptors
G protein
Extracellular fl uid
Cytosol
Receptor
Adenylatecyclase
Activates
Messenger
Protein kinase A
Protein+
ATP
PProtein-+
ADP
Response in cell
cAMP
GDP GTP
GTPGDP
ATP
g
b
1
2
3
4
5
6
G Protein-Linked Receptors
G protein
Extracellular fluid
Cytosol
Receptor Phospholipase C
Messenger
Protein kinase C
Protein kinase
ADP+
protein-P
Responsein cell
Response in cell(contraction, secretion)
Response in cell (contraction,metabolism, transport)
PIP2
IP3
DAG
Lumen ofendoplasmicreticulum
Membrane of endoplasmicreticulum
ATP+ protein
Protein-
Calmodulin
P
g
bGDP
GTP
GTPGDP
1
2
5b
43
5a
6c
6b
6a
Second Messenger Systems
Signal Amplification
Nervous Communication
Clinical Correlation: Cholera
Cholera Symptoms• Cholera toxins.• ______ w/ some ______.• _________.• _________.• _________.
He who struggles with us, strengthens our
nerves and sharpens our skills.
Our antagonist is our HELPER!
Edmund Burke
“Destiny is not a matter of chance; it’s a matter of choice. Its not a thing to
be waited for; IT’S A THING TO BE ACHIEVED!” William Jennings
Bryan
