describe a simple endocrine reflex for parathyroid hormone
stimulus - low plasma [Ca2+]
integrating center - parathyroid cell
output signal - parathyroid hormone
target - bone and kidney
response - increase bone resorption of Ca2+
-> increase kidney reabsorption of calcium
-> production of calcitriol leads to increase intestinal absorption of Ca2+
-> increase plasma [Ca2+]
describe a simple endocrine reflex for insulin
stimulus 1 - eat a meal
receptor - stretch receptor in digestive tract
integrating center - CNS and Pancreas (pancreatic beta-cells)
output signal - insulin
target - target tissues (insulin receptors -> Tyr-kinase activity-> increase glucose transporters)
tissue response - increase glucose uptake and utilization
systemic response - decrease blood glucose
stimulus 2 - increase blood glucose
integrating center -> pancreas
stimulus 3 - eat a meal-> glucose in lumen
integrating center - endocrine cells in small intestine
response - GLP-1 hormone -> signals pancreas to make more insulin
how can cells change their response to changes in [hormone]
- up regulation
-> try to maintain response despite low [hormone]
-> increase receptor number in response to sustained decrease [hormone] - down regulation
-> decrease receptor number in response to sustained increase [hormone]
-> usually involves endocytosis of membrane receptors
explain up/down regulation
- long term effects that take time to occur
- time required for endo/exocytosis; protein synthesis
- faster changes may be achieved with sensitization and desensitization
-> modification of existing receptors (de)phosphorylation to change their activity
-> total number of receptors does not change
explain how tropic hormones control secretion of another hormone
- many neurohormones of the hypothalamus and hormones of the anterior pituitary are tropic -> target another endocrine gland/cell to control hormone release
give an example of a tropic hormone
- thyrotropin releasing hormone (TRH) from hypothalamus
- causes release of thyrotropin thyroid stimulating hormone (TSH) from anterior pituitary
- causes release of thyroid hormones (T3, T4) from thyroid gland
what is synergism or “1+1>2”
- cells/tissues can be under the influence of multiple hormones and any given time
- hormonal interactions are not always predictable
- there is functional overlap of hormones
-> (adrenaline, glucagon, cortisol all increase blood [glucose]) - reasons for synergism are not well understood
- synergism may apply to any combination of chemical signals
what is permissiveness and an example
- if hormone A can’t produce its full effect without the presence of hormone B, then B is permissive for A
ex. reproductive hormone (A) requires thyroid hormone (B) - B does not need to have the same effect as A but is a requirement for A to work properly
- if only A alone = delayed reproductive development
- if only B alone = no reproductive development
explain how hormones can be functional antagonists
- hormones with opposite actions are considered functional antagonists
- opposite actions on the same systems
ex. insulin (decreases blood [glucose]) vs glucagon and growth hormone (increase blood [glucose]) - functionally antagonistic hormones don’t need to share receptors or signaling pathways
ex . insulin increase # of glucose transporters and glucose uptake, growth hormone decreases # of insulin receptors
explain how insulin and glucagon have antagonistic functions on blood [glucose]
- Insulin (released when blood glucose is high)
- Secreted by β-cells of pancreas.
- Lowers blood glucose by:
->Increasing glucose uptake into cells (especially muscle & fat).
-> Stimulating glycogen synthesis in liver & muscle.
->Promoting fat storage and protein synthesis. - Glucagon (released when blood glucose is low)
- Secreted by α-cells of pancreas.
- Raises blood glucose by:
-> Stimulating glycogen breakdown (glycogenolysis) in the liver.
-> Stimulating glucose production from non-carbs (gluconeogenesis).
-> Promoting fat breakdown for energy.
what is the relationship between ligands, agonists and antagonists
- a ligand that binds to a receptor and enhances its activity is an agonist for that receptor
- a ligand that binds to a receptor and inhibits its activity is an antagonist for that receptor
what are some examples of a ligand, agonist, and antagonist
- serotonin = the primary ligand activates a receptor
- psilocin = an agonist also activates the receptor
- clozapine = an antagonist blocks receptor activity
- target cell response determined by receptor and intracellular signaling pathways, not on the ligand
-> an agonist may have opposite effect in different tissues
ex. adrenaline dilates blood vessels in skeletal muscle but constricts blood vessels in intestines
what is specificity
- receptors may show preference for a particular ligand or type of ligand
- very specific -> bind very few ligands
- non specific -> able to bind many different ligands (not all at the same time)
- ligands can also show specificity for receptors
(important for drug developments)
what is competition
- multiple ligands may compete for the same receptor active site
- usually one ligand binds better than the other (higher affinity)
- overall effect of each ligand tends to be reduced compared to if they were the only one (since they each bind fewer receptors)
what is a competitive antagonist and an example
- same binding site on receptor as agonist
- can be overcome by increase [agonist]
ex. the GLUT transporter brings glucose across cell membranes
-> maltose is a competitive inhibitor that binds to the GLUT transporter but is not itself carried across the membrane
what is a non-competitive antagonist and irreversible antagonist
- different binding site on receptor (allosteric site) than agonist
- bind to same active site but cannot unbind, permanently taking receptor out of the equation (covalently bound)
- cannot be overcome by increase [agonist]
explain dose response curves and saturation
- % response depends on [agonist] and increases with % of receptors bound to agonist
- if [agonist] is high enough, receptors will be saturated and response is maximal
- sigmoidal curve on semilog scale allows easy measurement
what is EC50
- [agonist] producing 50% of the max response
explain competitive antagonists and dose response curves
- competitive antagonist make it more difficult for agonist to bind and elicit response
- max response can still be achieved with increase [agonist]
- increase EC50 with increase [antagonist]
explain non-competitive antagonists and dose response curves
- non competitive antagonists either change availability of binding site or irreversibly block binding site
- antagonistic effect cannot be overcome by increase [agonsit]
- decrease max possible response with increase [antagonist]
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