Midterm 2: Cell Communication Slides Flashcards
Hormones (general def. and 2 examples)
Long-range chemical messengers secreted into the bloodstream by endocrine glands in response to a signal, and carried in the blood to other sites where they affect target cells
-e.g., insulin and adrenaline
Paracrine signals/local mediators (def. and 2 examples)
Released by cells into the extracellular medium in their neighborhood and act locally
-e.g., histamine, epidermal growth factor (EGF)
Neurotransmitters (def. and example)
Chemical messengers that diffuse across synapses (small distance) to target cell
-e.g., acetylcholine
Key characteristic of target cells
Must have appropriate receptors to bind hormone and induce physiological response
Describe the endocrine system.
Composed of endocrine glands located throughout the body, and generally regulates activities that require duration rather than speed
What secretes hormones into the blood?
Endocrine glands
What are the types of hormones?
Peptides, amines, steroids
Describe peptides.
They comprise most hormones, including those secreted by the hypothalamus, anterior and posterior pituitary, pancreas, and parathyroid
Describe amines.
Derived from tyrosine (amino acid); includes hormones secreted by thyroid gland and adrenal medulla (catecholamines)
What are catecholamines?
Adrenomedullary hormones
Describe steroids.
Neutral lipids derived from cholesterol; includes hormones secreted by adrenal cortex, ovaries, and testes. They are lipid soluble (lipophilic).
How are water-soluble hormones transported and where are their receptors?
Dissolved in the plasma; receptors on the cell surface
How are lipophilic hormones transported and where are their receptors?
Bound to plasma proteins; receptors in the cytoplasm
Which types of hormones are water-soluble and which ones are lipophilic?
Water-soluble: peptides, proteins, catecholamines
Lipophilic: steroids
How do hormones produce their effects?
By altering intracellular protein activity
What happens when hormones bind with specific target cell receptors?
Starts chain of events in target cell which produces effects characteristic of that hormone
Classification of hormones based on receptors location
- Hydrophilic peptides and catecholamines are not soluble in lipids, so cannot cross lipid bilayer: bind to plasma membrane receptors
- Lipophilic steroids and thyroid hormones cross lipid bilayer and bind to intracellular receptors (inside cell)
Possible effects of epinephrine/adrenaline (4)
- Contraction of vascular smooth muscle
- Relaxation of respiratory airway smooth muscle
- Breakdown of liver glycogen
- Increased rate and force of contraction of heart
How hydrophilic hormones affect target cells (2)
- Most bind to cell surface receptor and produce second messenger molecule in target cell (hormone is 1st)
- Some bind to cell surface receptors and alter cell permeability by opening/closing ion channels
How lipophilic hormones affect target cells
Bind to intracellular receptors, activate specific genes (through transcriptional regulation in nucleus), causing new intracellular proteins to form and produce a characteristic physiological effect
Cortisol: what kind of hormone, produced where, made from what
Steroid hormone, cortex of adrenal gland, made from cholesterol
Types of cell surface receptors (3)
- Ligand-gated ion channels (e.g., acetylcholine receptor)
- G-protein-linked receptors
- Enzyme-linked receptors (e.g., insulin receptor)
What is the general idea behind G-protein-linked receptors?
Guanyl nucleotide binding proteins (G proteins) act as molecular switches that are active when GTP is bound and inactive with GDP due to action of intrinsic GTPase
How are G proteins classified with regards to subunits? What are the subunits?
Heterotrimeric: alpha, beta, and gamma subunits
How is cyclic AMP (cAMP) formed?
Formed from ATP by adenylyl cyclase, an enzyme that’s activated by a G protein
What do most effects of cAMP involve?
Binding to and activating cAMP dependent protein kinase (PKA), which phosphorylates specific proteins on serine or threonine residues, leading to physiological change
What do kinases and phosphatases do?
- Kinases phosphorylate molecules
- Phosphatases dephosphorylate molecules
What are the steps of the glycogenolytic cascade?
- Liver cells respond to epinephrine by activating G proteins
- G proteins activate cAMP synthesis
- cAMP activates a kinase cascade which releases glucose from glycogen
- Glycogen synthesis inhibited
- Kinase cascade amplifies epinephrine signal
What is the important of releasing glucose in the glycogenolytic cascade?
Key part of “fight or flight” response
Why are there so many steps in the glycogenolytic cascade?
Amplification: each epinephrine binding to a receptor on liver plasma membrane can release 10,000 molecules of glucose into bloodstream
Overview of inositol lipid signaling pathway
Phosphatidylinosital 4,5-bisphosphate cleaved by phospholipase C after receptor activation of a G protein to form 2 intracellular messengers
What are the two intracellular messengers formed in the inositol lipid signaling pathway and what do they do?
- Diacylyclycerol: activates protein kinase C
- Inositol trisphosphate (IP3): releases calcium from ER; is polar molecule
How is calcium concentration in the cytoplasm intentionally kept low?
Active transport, both out of the cell and into the ER
What happens once a signal triggers Ca2+ channels to open?
Ca2+ concentration quickly rises to 100x the resting concentration
Where do calcium ions bind?
To a specific calcium-binding protein called calmodulin, which can activate Ca2+-dependent protein kinases
Basic elements of cell signaling process (4)
Signaling cell, signaling molecule (wide variety), receptor (cell surface or intracellular), target cell response (cell-dependent)
Cell communication (def.)
How cells send and receive signals and how a cell responds after it receives a signal
4 examples of signal transduction pathways
- Nitric oxide pathway (more detail elsewhere)
- Growth factors: signal to nucleus and affect cell division via small G protein (ras)
- Sense of smell: odorant molecules activate G protein and cause cAMP to open ion channel
- Apoptosis: programmed cell death
General overview of nitric oxide signal transduction pathway
Nitric oxide (NO, gas) is intracellular messenger that links affects of acetylcholine to relaxation of smooth muscles of blood vessels
Steps in NO signal transduction pathway
- Acetylcholine acts on endothelial cells, stimulates IP3 pathway to produce Ca2+ influx
- Stimulates NO synthase to produce NO from arginine
- NO diffuses to underlying smooth muscle cell
- Stimulates guanylyl cyclase, produces cGMP (another intracellular messenger)
- cGMP stimulates kinase cascade leading to lowering of intracellular Ca2+, and muscle relaxation
What is nitric oxide in smooth muscle relaxation?
Second messenger
Why is the NO signaling pathway important?
NO formation from L-arginine by vascular endothelium important in blood pressure regulation and hypotensive actions of acetylcholine; by keeping small blood vessels dilated, blood pressure decreases
What is a Ras protein and how does it behave?
Monomeric G protein; behaves similarly to alpha subunit of heterotrimeric G proteins
What is Ras involved in and why are Ras mutations significant?
Involved in signaling cascade of growth factors that promote cell division; Ras mutations occur in many human tumors (esp. in pancreas, colon, bladder)
What is the function of intrinsic GTPase and what does it normally do to Ras?
Function is to hydrolyze bound GTP to GDP; it normally turns off Ras
What is the effects of mutations that impair GTPase?
Keep Ras active and over-stimulate cell division, leading to cancer
What are terms for mutated ras and normal ras?
- Mutated ras: oncogene (tumor-promoting gene)
- Normal ras: proto-oncogene
Steps in the “sense of smell” pathway
- Odorant molecules activate G protein, which activates cAMP synthesis
- cAMP synthesis causes ion channels to open
- Change in ion concentrations generates action potential that travels along olfactory nerve to brain
- Brain perceives signal as a scent
What is apoptosis?
Programmed cell death, where cell dies neatly without damaging its neighbors
What is the importance of apoptosis?
Normal part of development and aging, and it’s a homeostatic mechanism to maintain cell populations in tissues
Steps (general) of apoptosis mechanism
- Cysteine proteases (caspases) are activated
- Triggers complex cascade of events (proteolysis) leading to cell death
What is an important cell surface death receptor?
Fas
What molecules can trigger apoptosis (and how)?
Tumor necrosis factor (TNF) and other ligands can trigger it by binding to their receptors
Why would drugs want to target cell signaling pathways? Give example of drug that does so.
Almost all known diseases involve dysfunctional signaling pathways. Example is Viagra
How does Viagra generally work?
Inhibits cyclic GMP phosphodiesterase (an enzyme)
