Chapter 5

Chemical Messengers
Human Physiology
Dr. LeeShawn D. Thomas, M.S., Ph.D.
leeshawn.thomas@famu.edu

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 President Of 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 Jxs ___________ channels that allow ions and small mols 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

Indirect communication Through Chem Messengers

__________________ 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 .

Intercellular Communication

Figure 5.1b

Chemical Messengers
Chem messs are based on their f(x) and chem structure. Functional Classification of chem messs 4 main categories Paracrine _________ Neurotransmitter _________

 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); PDGF i.e. Clotting factors (clot blood). Interleukins i.e. __________ (commun in Immune sys) Interferons i.e Histamine released by ______ cells & causes allergic rxs & ____________. Inflamattion redness and ______ blood flow fluids leak out of _________ into tissue (swelling)

ICE & Temp

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). 1980s Pfizer begin making $180 million a year from the drug.

Tumor

Capillary

Avastin

Targeted Therapy

Velociximab

Normal

Blocking 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 chems 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 messs _______ ______ Amines ________/Proteins Steroids ____________

Amino acids
4 amino acids are called neurotransmitters b/c they f(x) in the brain and spinal cord. _________ Part of 20 Aspartate Amino acids _________ Gamma aminobutric acid (GABA). Amine Messengers Derived from amino acids NH2 Include a group of compounds called catecholamine (catechol group) made from _________.

 ___________ Norepinephrine (Noradrenaline) Epinephrine (Adrenline)

Catecholamines (Derived from Tyrosine)

Serotonin - __________ Thyroid hormone - tyrosine Histamine - ___________

Peptides/Protein Messs
Most chem messs are polypeptides. Peptides < less than 50 amino acids; Polypeptide > 50 amino acids.

Steroids
Derived from _____________. All steroid f(x) as _________. _________ & Lipophilic properties.

COOH HO CH2 Tyrosine b-hydroxylase OH HO Catechol group OH HO CH2 Dopamine b-hydroxylase OH HO CH OH Phenylethanolamine N-methyl transferase (PNMT) OH HO CH OH CH2 NH CH3 Epinephrine CH2 NH2 Norepinephrine CH2 NH2 Dopamine CH2 Dopa decarboxylase COOH C H NH2 L-Dihydroxyphenylalanine (L-dopa) C H NH2 Tyrosine

 Synthesis & Release of Chem Messs The 4 a.as that f(x) as neurotransmitters must be synthesized in the neuron.

Glucose

3-Phosphoglycerate

__________

Aspartate

________

GABA

Steroids Catalyzed by enzs 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.

Eicosanoids Are derivatives of arachidonic acid from membrane phospholipids. Made on demand and released immediately b/c they are lipophilic.

Dose of a drug has Diff effects 85mg - inhibit clots 350 - inhibit pain
Aspirin Blocks Inflam Blocks _________

VIOXX Chronic Pain & Inflamm

(Inflamm) (blood clot) (blood clot)

(Inflamm)

Transport of Messs
Paracrine Autocrine Neurotransmitters

Utilizes diffusion

 Hormones Use bloodstream Dissolved _______ Protein

A) Corticosteroid binding globulin B) _________ non specific

< 1% hormone in dissolved in plasma

H Pr H + Pr
H-amt of free proteinPr-carrier protein;
Half Life time it takes the hormone in blood to degraded.

 _______(degraded) _______ (excrete). Soluble in H2O (_____ half life).

Soluble in Lipid (_____ half life); protected by ________ protein.

Signal Transduction
Chem messs 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 messs can bind to more than one ________ and these messs 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 recepts for more than one type of mess i.e. skeletal muscle have recepts 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. (____ messs conc) Down-regulation - in the # of recepts when messs 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

Signal Transduction Mechanisms

Peptide and Proteins

Rough endoplasmic reticulum

mRNA
1 Polypeptide

Golgi apparatus

Prepropeptide Propeptide Propeptide 2 3 4

Propeptide 5

Peptide

Cleaved amino acids

Secretory vesicle Transport vesicle

Cleaved amino acids

Smooth endoplasmic reticulum

Prepropeptide

Propeptide Cleaved amino acids

Peptide Cleaved amino acids

(a) Peptide synthesis

Intracellular Mediated Response

Lipophilic messenger Extracellular uid Diffusion

1a

Nucleus Target cell

1b
Nuclear receptor

DNA

5 Proteins 4 Ribosome

Cytoplasmic receptor

3 2 Hormonereceptor complex

mRNA
mRNA Nuclear envelope Nuclear pore

Hormone response element (HRE)

 Channel-Linked Receptors

 Enzyme-Linked Receptors

 G Protein-Linked Receptors
Extracellular Messenger 1 Receptor Adenylate cyclase uid

2 GDP G protein

g GDP

GTP 3 cAMP ATP 4 Protein kinase A 5 Protein + ATP Protein+ ADP 6 P Activates

GTP

Cytosol

Response in cell

Second Messenger Systems

Messenger 1 Receptor Phospholipase C Extracellular uid 3 4

GDP

2 b g GTP

5b

PIP2 IP3

DAG Protein kinase C

G protein

GDP

GTP ATP+ protein

5a ADP + protein6a Response in cell 6b

6c Calmodulin

Lumen of endoplasmic reticulum

Protein kinase Response in cell (contraction, secretion)

ProteinMembrane of endoplasmic reticulum

Response in cell (contraction, metabolism, transport)

Cytosol

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; its a matter of choice. Its not a thing to be waited for; ITS A THING TO BE ACHIEVED!

William Jennings