Chapter 7: Cell Communication Flashcards
Three Signaling Systems
- Hormones: long-range chemical messengers, secreted into blood by endocrine glands in response to signal and carried in blood to target cells (adrenaline)
- Paracrine signals: (local mediators) released by cells into ECM in neighborhood, act locally (histamines, EGF)
- Neurotransmitters: diffuse across synapses (acetylcholine)
What secretes hormones?
endocrine glands
What do hormones act on?
target cells with receptors to bind and create a physiological response
What is the endocrine system composed of?
endocrine glands
What does the endocrine system do?
regulates activities that require duration, rather than speed
What are the 3 types of hormones?
Peptides, Amines, Steroids
What are peptides?
comprise most hormones, including those secreted by hypothalamus, anterior/posterior pituitary, pancreas, and parathyroid
What are amines?
derived from amino acid tyrosine, include hormones secreted by thyroid gland and adrenal medulla
What are catecholamines?
Adrenomedullary hormones
What are steroids?
natural lipids derived from cholesterol, include hormones secreted by adrenal cortex, ovaries and testes. lipophilic
Water-soluble hormones v. Lipophilic hormones?
lipophobic: transported dissolved in the plasma, whereas lipophilic: transported largely bound to plasma proteins
How do hormones produce their effects?
By altering intracellular protein activity –> bind with specific target cell receptors –> start a chain of events in the target cell
What are two groups of hormone receptors?
- Plasma Membrane Receptors
2. Intracellular Receptors
What are Plasma Membrane Receptors?
hydrophilic peptides and catecholamines, being poorly soluble in liquid, are unable to cross the lipid bilayer and thus bind to THESE receptors
What are Intracellular receptors?
Lipophilic steroids and thyroid hormones cross the lipid bilayer and bind to THESE
What 4 effects does epinephrine (an adrenal medullary catecholamine) produce?
- contraction of vascular smooth muscle
- relaxation of respiratory airway smooth muscle
- breakdown of liver glycogen
- increased rate and force of contraction of heart
Hormones affect target cells by altering activity of proteins within the cell:
- most hydrophilic hormones binding to cell surface receptors produce a second messenger molecule within the target cell (hormone = “first” messenger)
- a few hydrophilic hormones following binding to cell surface receptors, alter cell permeability by opening or closing particular ion channels
- Lipophilic hormones through binding to intracellular receptors, activate specific genes (through transcriptional regulation within nucleus), leading to the formation of new intracellular proteins which produce a characteristic physiological effect
3 Types of cell surface receptors:
- Ligand-gated ion channels (acetylcholine receptor)
- G-protein-linked receptors (guanyl nucleotide binding proteins (G proteins) act as molecular switches; activate when GTP is bound, inactive with GDP due to action of intrinsic GTPase
- Enzyme-linked receptors (insulin receptor)
Ligand-gated channels (example)
acetylcholine receptors
G-protein-linked-receptors
(guanyl nucleotide binding proteins (G proteins) act as molecular switches; activate when GTP is bound, inactive with GDP due to action of intrinsic GTPase
Enzyme-linked receptors (example)
insulin receptor
How is cAMP formed
formed from ATP by adenylyl cyclase, an enzyme that is activated by a G protein
How does cAMP affect cells?
cAMP binds to and activates cAMP dependent protein kinase (PKA)
What does activated PKA do?
It phosphorylates specific proteins on serine or theronine residues –> physiological change
Explain the role of cAMP in the glycogenolytic cascade? (slides 8/9 cell comm 2)
Liver cells respond to epinephrine by activating G proteins –> activate cAMP synthesis–> cAMP activates kinase cascade which releases glucose from glycogen (glycogenolytic cascade) & @ same time, glycogen synthesis is inhibited–> kinase cascade amplifies epinephrine signal–> release of glucose is a key part of the “fight or flight” response to epinephrine
Why are there so many steps in the Glycogenolytic cascade?
Amplification.
-Each molecule of epinephrine binding to its receptor on liver membrane can release 10,000 molecules of glucose in bloodstream
What turns off the glycogenolytic cascade?
-Epinephrine levels decrease (dissociates from receptor) –> G protein becomes inactive–> cAMP levels decrease due to action of cAMP phosphodiesterase–> Phosphatases dephosphorylate key enzymes in cascade
Phospholipase C cleaves Phosphatidylinositol 4,5 -biphosphate following receptor activation of a G protein. What 2 intracellular messengers are formed?
- Diacylyglycerol
2. Inositol triphosphate (IP3)
What is diacylyglycerol?
activates the protein kinase C
What is inositol trisphosphate?
IP3, releases calcium from the ER
What is phosphatidyinositol 4,5 biphosphate (PIP2)?
a phospholipid molecule involved in signal transduction
What is an example of an intracellular messenger?
Calcium
What is calcium’s concentration in the cytoplasm?
0.1 uM
How is calcium’s concentration kept low?
via active transport (in the cell & out of the cell)
What happens when a signal triggers Ca2+ channels to open?
[Ca2+] rapidly rises to up to 100 times the resting concentration
Calmodulin
the calcium-binding protein to which calcium ions bond, which can activate Ca2+ dependent protein kinases
Define cell communication
how cells send and receive signals and how a cell responds after it receives a signal
how do cells communicate?
by using a variety of chemical signals that bind to specific receptors on the target cell
What are the 4 elements of cell signaling process?
- signaling cell
- signaling molecule (wide variety: hormones, pheromones, growth factors, gases (NO))
- Receptor (cell surface or intracellular depending on nature of what is binding)
- Target cell response (depends on cell)
What is the benefit of signaling cascades?
provide amplification (ex: glycogenolytic cascade converts epinephrine to glucose)
Nitric oxide (NO)
via signal transduction causes vascular smooth muscle relaxation and vasodilation of blood vessels
Growth Factors
signal to the nucleus and affect cell division via a small G protein (ras)
Sense of smell
Occurs via odorant molecules activating a G protein and causing cAMP to open an ion channel
Apoptosis
programmed cell death
What does acetylcholine do ?
relaxation of smooth muscles of the blood vessels
What happens when acetylcholine acts on endothelial cells? (slides 10/11/12)
stimulates the IP3 pathway to produce an influx of Ca2+, which stimulates NO synthase to produce NO from arginine–> NO diffuses to the underlying smooth muscle cell, where it stimulates guanylyl cyclase leading to production of another intracellular messenger, cGMP –> stimulates a kinase cascade leading to lowering of intracellular Ca2+ and muscle relaxation
What role does NO signaling pathway play?
NO formation from L-arginine by vascular endothelium regulates blood pressure and hypotensive actions of acetylcholine
How is blood pressure reduced?
By keeping small blood vessels dilated.
What is Ras?
Ras is a monomeric G protein, that behaves similarly to the alpha-subunit of G proteins
- involved in the signaling cascade of growth factors which promote cell division
- Ras mutations occur in human tumors (pancreas, colon, bladder)
What normally turns Ras off?
intrinsic GTPase (which hydrolyzes bound GTP to GDP)
What keeps ras active?
Mutations which impair GTPase keep ras active and over-stimulate cell division –> cancer
What is the mutated ras gene called?
ONCOGENE (tumor-promoting gene)
What is normal ras called?
Proto-oncogene
How does sense of smell occur?
Via odorant molecules activating a G protein and causing cAMP to open an ion channel–> generates an action potential which travels along the olfactory nerve–> brain
What is apoptosis?
Programmed cell death (cell dies without damaging its neighbors); normal part of development; necessary to maintain cell populations in tissues
What happens when cysteine proteases are activated?
triggers a cascade of events (proteolysis) leading to death of cell
What is proteolysis?
complex cascade of events that leads to cell death
What is Fas?
important cell surface death receptor
What does Tumor necrosis Factor (TNF) do?
can trigger apoptosis through binding to their receptors
What does the drug VIAGRA do?
inhibits cyclic GMP phosphodiesterase
