chapter 5 vert phys students)

Chapter 5 Chemical Messengers

Dr. LeeShawn D. Thomas, M.S., Ph.D.leeshawn.thomas@famu.edu

Human Physiology

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