Receptors, signals ans responses Flashcards
why is cell communication important?
there are lots of tissues, organs + cell types in the human body - need to keep responding to changes in environment.
Growth, infection, blood glucose, wounds, and time to die.
3 important steps in cell signalling
signal, receptor, response
cellular response without a signal can lead to
cancer
over reacting immunity signals
inflammatory response
not responding to immunity signals
immunodeficiency
which cells make insulin?
Beta cells in the islets of lagerhands, located in the pancreas
what do the alpha cells in the pancreas make?
glucagon
what happens when there are low blood sugar levels?
glucagon is released, tells the cells that you need fat cells to start releasing their energy source to maintain blood sugar levels
ENDOCRIN SIGNALLING
hormone secretion into the blood by an endocrine gland - to act on distinct target cells in the body
PARACRINE SIGNALLING
cells secrete signals close to the target cells
what are direct contacts?
in the epithelial sheet forming connections between cells.
they detect signals from neighbouring cells and the ECM (how rigid is the ECM)
what is synaptic signalling
where nerve cells release neurotransmitter into the synaptic cleft - taken up and causes a response in the target cells
example of hormones that use endocrine signalling
testosterone and insulin
examples of paracrine signalling
growth factors, cytokines (immune cells), NO
what are neurotransmitters derived from/
amino acids
what are steroids derived from?
cholesterol
example of a small molecule signal
adrenaline
examples of peptide hormones
hCG, LH
insuline
example of a steroid hormone
testosterone
what are the 4 main receptor types
steroid receptors, G protein coupled, ligand gated channels, enzyme linked
what are 2 main types of repsonsed to signals
Turn genes on or off
Modulate the activity of cellular proteins
what are steroid receptors?
they are transcription factors/activators that turn genes on and off
are steroid lipophilic or hydrophilic?
lipophilic
so they diffuse across cell membranes
where would you find a steroid receptor?
in the nucleus or cytoplasm
sequence of events for steroid receptors
2 steroid receptors – form dimer – only in this form can the steroid recpetors act as transcription factor – need to bind to enhancer – induce recruitment of standard transcription machinery to the proton region (initiation complex) and then polymerases transcribe the gene
What does the enhancer region do?
coordinated signals and timing
what provides specificity for steroid receptors?
Different steroid receptors bind different steroids and different steroid receptors different enhancers
which drug is used for medical abortions?
Mifepristone
how does Mifepristone work in abortions?
receptor antagonist, antagonises the progesterone receptor, stop the cells being able to produce progesterone, progesterone cannot maintain pregnancy
what is cushing’s syndrome?
over production of cortisol (adrenal gland tumours)
how would you treat cuttings syndrome?
Making too much steroid – inhibitors which inhibit pathway where cholesterol is turned into cortisol – blocking the formation of signal
using ketonazole metyrapone
what drug would you use to break cushings
Ketoconazole Metyrapone
ligand gated ion channels open in response to…
a signal to allow ions to flow through
what type of receptors do neuromuscular junctions use?
ligand gated ion channels
what happens in neuromuscular junctions?
Ach is released into the synaptic cleft from the vesicles in the presynaptic knob, when the vesicles fuse with synaptic membranes they bind to the receptors and allow ions to flow through the channels into the muscle
which enzyme mops up/breaks down Ach?
Acetylcholinesterase
how does botulinum toxin work to stop muscle movement?
it inhibits Ach release, so there is no AP and so no muscle contraction
what affect does nerve gas have on muscle contraction and why?
nerve gas inhibits AchE - Ach can’t be broken down so you get constant signal - excessive muscle contraction
what fraction of human genes code for GPRCs
1/20 genes
what percentage of pharmaceuticals work on GPRCs
40%
examples of what some GPRCs do
Immune modulators (chemokines), taste and smell, hormones (adreneline) synaptic (some) , eyes use to detect light
how does adrenaline affect skeletal and cardiac muscle - lung bound to GPRCs
More energy
Increased blood and air (vasodilation)
Weaker contraction (smooth muscle) Stronger contraction (skeletal muscle)
how does adrenaline affect gut and skin bound to GPRCs
Less energy Less blood (vasoconstriction)
Stronger contraction (smooth muscle)
the same hormone can bind to
different receptors
where would you find a1 adrenoreceptors
in the GI tract
what response do a1 receptors have to adreneline
smooth muscle contraction and casoconctriction
where would you find B1 arenoreceptors
heart
what response do B1 adrenoreceptor have to adrenaline
inc. heart muscle contractility
where would you find B2 adrenoreceptors
in the lungs
what response would you get if B2 receptors were stimulated with adrenaline
smooth muscle relaxation and vasodilation in the lungs
GPRCs are molecular
switches
On = bound to GTP Off = bound to GDP
GTPases
GPRCs are coupled to
a heterotrimeric subunit
which part of the heterotrimeric subunit binds GTP/GDP
the a part
in GPRCs what amplifies the signal
second messengers - eg cAMP
how do B adrenergic receptors in heart, skeletal and lungs work
G protein receives signal, Gas dissociates from the other 2 when bound to GTP, stimulates adenylate cyclase to convert ATP to cAMP very quickly, which then activated PKA which will phosphorylate target proteins
what is so beneficial about second messengers
small , produced rapidly , produce lots cellular response
what do kinases do?
add phosphates to things
what do specific Specific serine/ threonine/ tyrosine residues do?
regulate activity and localisation
what is the chemical formulation of phosphate?
PO4
what do beta blockers do?
heart conditions, high blood pressure combating
what is an example of B adregenergic receptor antagonist
propanolol
what do B antagonists end in
-olol
what is a B antagonist in the lungs - for asthma
salbutamol
what turns off the signal in the in Gas
phosphodiesterase
converts cAMP back to AMP
which phosphodiesterase inhibitor is used to treat heart failure? how does this work?
PDE 3 inhibitor
increase the amount of cAMP
how does the Kinase linked receptor work?
Outside portions bind – dimerise – brings kinases domains close together – phosphorylate one another
Lots molecules in cell – recognise phophorylated target site – recruitment to receptor – turn on G protein
This G protein is called ras
what is ras?
a small GTPase
in the kinase linked receptor what is the purpose of Ras?
induce a MAP cascade then the Pi binds to transcription factor (transcription factors are phosphorylated) and then move into the nucleus
what is the function of perception in cancer?
stops EGF binding to its tyrosine kinase receptor - so the to receptors cannot phosphorylate one another - cannot promote growth inside the
what would you use if you had a mutation in Ras so that you cannot turn it off?
inhibitor that block MAP kinase function
how does PKA affect cardiac muscle?
phosphorylates L type calcium channel - Ca2+ flows in and then myosin chains contract, muscle contraction.
