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Chemical Messengers
Human Physiology
Dr. LeeShawn D. Thomas, M.S., Ph.D.
leeshawn.thomas@famu.edu
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
With a good education and HARD WORK, combined with HONESTY and INTEGRITY, THERE ARE NO BOUNDARIES!
Dr. LaSalle Leffall, Jr. M.D.
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
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)
R.I.C.E.
R = Rest, I = Ice, C = Compress E = Elevate. Heat causes ___________. Ice causes _________.
Tumor
Capillary
Avastin
Targeted Therapy
Velociximab
Normal
Blocking a protein
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.
Figure 5.2b
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 ________.
Figure 5.2d
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 _________.
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 _________
(Inflamm)
Transport of Messs
Paracrine Autocrine Neurotransmitters
Utilizes diffusion
H Pr H + Pr
H-amt of free proteinPr-carrier protein;
Half Life time it takes the hormone in blood to degraded.
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).
mRNA
1 Polypeptide
Golgi apparatus
Propeptide 5
Peptide
Prepropeptide
1a
1b
Nuclear receptor
DNA
5 Proteins 4 Ribosome
Cytoplasmic receptor
3 2 Hormonereceptor complex
mRNA
mRNA Nuclear envelope Nuclear pore
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
GDP
2 b g GTP
5b
PIP2 IP3
G protein
GDP
6c Calmodulin
Cytosol
Signal Amplification
Nervous Communication
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
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William Jennings