ch 5 chemical signaling

Question 1

direct intercellular communication

Answer 1

• direct communication through gap junctions
• a connexon is a protein channel that connects 2 cells in a gap junction.
• ex: two rooms in a hotel that connect by a door thats always open.
• this is only good for short-distance signaling, but it is very very fast!

Question 2

indirect intercellular communication

Answer 2

• communication via chemical messengers
• where a secretory cell releases a chemical messenger that binds to a receptor on a target cell

Question 3

chemical messengers: paracrine

Answer 3

• different types of chemical messengers
• paracrine signaling involves 2 cells that are very close to each other but are not touching

Question 3

chemical messengers: neurotransmitters

Answer 3

• identical to paracrine signaling, only the secretory cell will always be a neuron and the target cell will either be another neuron, gland, or muscle.
• very fast!
• ex: how fast it takes to move hand off hot stove! that neurotransmitter signaling
• synapse: the junction between a neuron (presynaptic) and its target cell (postsynaptic)

Question 4

chemical messengers: endocrine signaling

Answer 4

• endocrine=hormone
• involves a hormone being released into the bloodstream
• every living cell in your body is less than a millimeter from the nearest capillary
• long distance traveling but takes longer

Question 5

pros & cons: endocrine signaling

Answer 5

• pro: its great for long distance signaling. a hormone released from the pancreas can affect cells in your feet. it lasts linger than paracrine or neurotransmitter signaling. insulin will lower your blood sugar for hours
• con: its slow to take effect. after a meal, insulin lowers your blood sugar, but how long does that take: several minutes. meaning, endocrine signaling is not the ideal way to control things like your reflexes, that require speed

Question 6

ligand - receptor interactions

Answer 6

• paracrine, neurotransmitters, and hormones are ligands that bind receptors
• a ligand is anything that binds to a receptor
• the shape of the ligands and the receptor, both ligand A and B are specific for that receptor
• the charges on the ligands determine which receptor they go with.
• ex: receptor has a positive charge and ligand B has a higher affinity for the receptor bc its charge is neg and ligand A has a pos charge
• if the ligands have to compete, ligand B will win

Question 7

endocrine signaling

Answer 7

• polar (unequal sharing of electrons, hates fat) and charged molecules are hydrophilic <3 and will dissolve in water
• nonpolar (equal sharing of electrons, <3 fat) molecules are hydrophobic and will not dissolve in water, they will repel it
• blood is mostly water, if the endocrine messenger is hydrophilic it will dissolve in the bloodstream
• if the messenger is hydrophobic, it will mostly be bound to carrier proteins to shield the messenger from the water in the bloodstream

Question 8

receptor proteins

Answer 8

• a target cell receives a signal bc it has receptor proteins specific to it on the plasma membrane or inside the cell
  -nonpolar (equal sharing of electrons, hates fat) signal molecules such as steroid hormones can penetrate the plasma membrane and interact with receptors inside the cell
• the type of messenger determines where the receptor is found on the target cell.
• plasma mem is mostly nonpolar (only polar cannot dissolve through). the receptor for polar messengers will be found on the outside of the plasma membrane on a target cell bc of this.
• for small nonpolar messengers, the receptor in a target cell is found inside the cell bc these messengers can dissolve through the plasma mem.

Question 9

receptor properties

Answer 9

• specificity: each type of receptor only binds one type of ligand/molecule (shape & size)
• affinity: strength of binding between a ligand and its receptor (charge)

Question 10

receptor activation depends on:

Answer 10

• concentration of ligand: add more ligand (more ligand increases the likelihood that a ligand will bind to a receptor
• expression level of receptor: add more receptors (more receptors will have the same effect as more ligand (binding increases)
• affinity of receptor for ligand: increase the affinity between the ligand and the receptor (if they are more attracted to each other, they will be more likely to make contact with each other

Question 11

relationship between ligand concentration and receptor

Answer 11

• if you add more ligand you will activate more receptors
• once all receptors are bound, adding more ligand will not have any effect
• ex: 100 locks that you want to open as quick as possible adding more keys will help but once you have 100 keys adding more wont help at all

Question 12

how can number of receptor change?

Answer 12

• receptor synthesis (make more receptors for ligands to bing to) <–> receptor turnover (degradation) (destroying of receptors by sending them to the lysosome (cleaner of the cell) where they are broken apart

Question 13

how can number of receptors change?

Answer 13

• speed of synthesis
• upregulation: increase in receptor synthesis (increase of speed of receptors being made)
• downregulation: decrease in receptor synthesis (slows down receptors being made)
  *deals with up&down regulation not turnover (destroying of receptors)
• normally the amount of receptors = amount of ligands
• in some cases, if more ligand becomes available, a cell will make receptors more quickly (upregulation)
• in some cases, cells will make receptors more slowly if less ligand becomes available

Question 14

drug interaction

Answer 14

• every addictive drug available today takes advantage of pre-existing receptors in the human body
• binding of the drug to these receptors often activates a network of dopaminergic cells in the mesolimbic region of the brain that are involved in emotional reward
• all addictive drugs are artificial ligands that bind to receptors in the body (over and over, causes compulsive behavior and becomes overly active and produces excess dopamine, making it more difficult to quit.
  another ex of positive feedback

Question 15

drug addiction

Answer 15

• opiates: painkillers such as codeine, morphine, oxycodone, oxycontin, heroin, etc
• activate natural G-protein coupled receptors for endorphins in the brain. endorphin concentration is usually extremely low
• triggers receptor turnover and downregulation as well as desensitization resulting from functional un-coupling of G protein receptors to their effector molecule

Question 16

drug addiction pt 2

Answer 16

• endorphins are found in the human body to help you deal with MINOR pain, like a toothache or stubbing your toe, or running 5 miles. these are found in VERY VERY LOW concentrations
• bc: we were never meant to be pain-free. pain has a purpose. it tells us to stop doing what you are doing before you will yourself.
• so, there are not enough endorphins in your body to make the pain go away when you have a major injury like 3rd degree burn or broken leg.
• opiates bind to endorphin receptors but the concentration of opiates in just a single pain pill is hundreds to thousands of times the concentration of natural endorphins in your body
• so, when you take an opiate for the first time, it binds to all of the endorphin receptors on your cells producing an enormously euphoric “high”
• but, your body recoils from this and immediately begins to destroy a lot of these endorphin receptors bc we were never meant to be pain-free
• so, the next time you taken an opiate the “high” isnt nearly as intense as the firs time so people take more which leads to addiction
• typically when a heroin or oxy addict overdoses, they take such a large quantity of the drug bc they have so few endorphin receptors left. its difficult to even get high at all bc your body downregulates these receptors bc you can live without endorphin. it will be painful, but life threatening and its the safest course of action that your body can take

Question 17

opioid receptor turnover/downregulation

Answer 17

• with too much ligand around, your cells will begin to destroy endorphin receptors already on your cells

Question 18

nicotine addiction

Answer 18

• nicotine has an extremely high affinity for acetylcholine receptors in the brain. it essentially out-competes acetylcholine for these receptors
• cells that require acetylcholine for signaling respond by making more acetylcholine receptors and releasing much more acetylcholine
• most addictive drug in the world
• nicotine binds to receptors for the neurotransmitter acetylcholine. whats important is that nicotine actually has a higher affinity for the acetylcholine receptor than acetylcholine does and you cannot live without acetlycholine, so the receptor turnover/downregulation simply is not an option bc you cant deprive yourself of acetylcholine.
• only option is for your body to upregulate and make more receptors and to make more neighboring cells release more acetylcholine to out-compete nicotine for these receptors. this results in your needing more and more nicotine to recive the desired effect…then leads to addiction

Question 19

upregulation of receptors by nicotine

Answer 19

• your cells make more acetylcholine receptors and cause cells to release more acetylcholine. so overtime the amount of nicotine in your body essentially gets diluted, causing you to take in more and more of the drug

Question 20

nicotine addiction

Answer 20

• there is also evidence that increased the use of nicotine results in increased ability of an individual to metabolize nicotine. results in a shorter half-life of the drug (increases ability to metabolize nicotine
• it has been suggested that nicotine upregulates extracellular mechanisms for degrading the drug

Question 21

additional reason why nicotine is so addictive

Answer 21

• the more you expose yourself to nicotine, the more efficient your body gets at breaking the drug down before it even reaches your receptors
• suggests that nicotine upregulates mechanisms to beat the race vs acetylcholine ligands?
• meaning: a person who never smokes and a person who smoked for 20 years. both take one cigarette and draw bld from each. the non-smoker will have an extremely high levels of nicotine while the smoker will hardly have any

Question 22

mechanisms for drug tolerance

Answer 22

• pharmacokinetic tolerance: the result of lower concentrations of a drug actually reaching the receptor. could be caused by degradation, or increased metabolism of the drug (nicotine)
  ex: 20 year old smoker compared to first timer, body gets better at breaking down drug before reaching receptor
• pharmacodynamic tolerance: cellular mechanism that results in receptor downregulation/turnover (opiates), or upregulation (nicotine)
  number of receptors change
• this is why nicotine is more addictive than heroin. heroin uses only results in pharmacodynamic tolerance. nic use results in both tolerances^

Question 23

ligand properties

Answer 23

• chemical messengers which come from secretory cells
• agonist: ligands that bind to receptors and cause a biological response
  ex: acetycholine (agonist/good guy, nic antagonist (bad guy)
• antagonist: ligands that bind to receptors and do not cause a biological response
  antagonists may compete with agonists and decrease agonist binding and cellular response
• all nic really does is keeps acetylcholine from binding to receptor. nic just took a seat and did not do anything (biologically/physiological)
• ex: the lock is the receptor. the key is the agonist bc it unlocks the door. a piece of tape over the keyhole would be antagonist bc it prevents the door from unlocking.

Question 24

signal transduction REVIEW

Answer 24

• a series of events that occur as soon as the ligand binds to a receptor
• refers to intracellular mechanisms that mediate response of target cell to chemical messenger
• downstream of receptor-ligand binding
• lipophilic (lipid loving aka fat, anything that likes lipis will not like water, basically can dissolve in fat) messengers –> receptors typically intracellular (stay inside)
• lipophobic (lipid fearing, anything that fears lipids will like water) messengers –> receptors on membrane surface (fat fearing, once hit receptor stay on outside of cell mem)

Question 25

second messenger

Answer 25

• an intracellular messenger produced by the binding of an extracellular messenger
• the ligand is the first messenger
• if this first messenger is polar, all its able to do it bind to a receptor on the cell mem
• sometimes this results in the production of a second messenger inside the cell that essentially carries the signal to the nucleus

Question 26

second messengers

Answer 26

• second messengers are not needed for hydrophobic/lipophilic (fat loving) messengers bc these ligands can cross the membrane, they dont need a second messenger. they can go straight to the nucleus themselves
• polar hydrophilic/lipophobic need a messenger (second messenger in the cell)

Question 27

lipophilic signaling

Answer 27

• fat loving water hating messenger can cross the mem and either bind to receptor in cytoplasma or enter nucleus directly
• in either case, the cellular response is the same
• the cell increases gene expression/ protein synthesis

Question 28

membrane receptor-mediated signal transduction pathways

Answer 28

1. fast channel-linked (calcium, sodium, chloride, potassium etc)
2. enzyme-linked
3. G-proteins (slow channel-linked, cAMP, cGMP, phosphatidylinositol)
   - in orde for a receptor on the membrane to have an effect on the inside of the cell, it has to be connected to some sort of pathway
   - the receptor can act like an ion channel
   - the receptor can be connected to an enzyme that controls the production of a second messenger
   - the receptor can be connected to a G-protein

Question 29

fast channel-linked receptors

Answer 29

• simple fast process = change potential
• a lot of receptors for hydrophilic ligands are actually ion channels
• when the ligands binds, these channels open and allow ions to cross the membrane. this changes the membrane potential of the cell (this is the cellular response)

Question 30

enzyme-linked receptor

Answer 30

• the receptor for a hydrophilic ligand could be linked to an enzyme, specifically a kinase
• a kinase is an enzyme that adds a phosphate group to another protein and activates that protein
• when the ligand binds to the receptor, it causes 2 or more receptors to come together and form a dimer, this is called dimerization
• dimerization activates the kinase, which pohosphorylates several proteins inside the cell
• when the ligand binds to the receptor, it activates the kinase, which phosphorylates several proteins inside the cell
• these proteins being activated are kind of a like a domino effect, that produces some response in the cell

Question 31

G-proteins

Answer 31

• small intracellular proteins that link receptors with effector proteins
• receptors linked to G proteins are called G protein coupled receptors (GPCRs)
• have three subunits: alpha, beta, and gamma
• three types: ion channel regulating, enzyme inhibiting Gi, and enzyme stimulating Gs)
• the 3rd option for a receptor for a hydrophilic ligand is that it is connected to a g-protein (this is a small protein with 3 subunits)
• G-proteins basically bridge the gap between the receptor and another protein inside the cell that does something, this ic