Flashcards in Receptor Transduction Systems Deck (41):
what is signal transduction?
a process by which a cell converts a signal or stimulus into a response
what does signal transduction involve?
a sequence of biochemical reactions carried out by enzymes and linked through intracellular signalling molecules
what is a second messenger?
intracellular signalling molecules
what does the signalling cascade allow?
a single stimulus to be amplified, and/or expanded to produce multiple different responses
examples of responses produced by signal transduction
modulation of gene translation, hormone secretion, energy production, cell division and cell motion
why does gene translation effects lead to further longer term changes?
because genes are expressed as proteins, many of which are enzymes, transcription factors or other regulators of cellular activity
examples of intracellular second messenger signalling molecules
- cyclic nucleotides (cAMP, cGMP)
- calcium ions
- derivatives of phosphatidylinositoltriphosphate (PIP3): IP3 and DAG
what do second messengers regulate?
the function of specific cellular effectors commonly kinase or phosphatase enzymes
how do extracellular stimuli engage signal transduction pathways?
they engage it through 4 primary types of receptor
what are the two types of receptors?
cell surface transmembrane receptors and nuclear receptors
what are the cell surface transmembrane receptors?
- receptors linked to ion channels
- receptors couples to G proteins
- receptors couples to enzymes
what are nuclear receptors?
receptors that affect gene transcription
what do ligand-gated ion channels do?
they, upon ligand binding, open a pore in the membrane increasing permeability to specific ions
what kind of responses are consequence of this increase in the membrane permeability?
postsynaptic excitatory or inhibitory responses
what do voltage-gated ion channels respond to?
changes in membrane potential - underlies the action potential impulses that travel along nerves
how are ligand-gated ion channels?
multimeric transmembrane receptors
what does multimeric mean?
A multiprotein complex is a group of two or more associated polypeptide chains
are ligand-gated ion channels specific?
they open pores for specific ions; commonly for cations (Na+ and K+)
what type of transport do ions undergo with ligand-gated ion channels?
passive transport (down the concentration or electrical gradient) - very rapid
how does the nicotinic acetylcholine receptors work?
1. receptor with 2 binding sites for ACh
2. agonist (ACh) binds
3. channel opens, ions pass through
4. antagonist inhibits binding of agonist (channel shut down)
other examples of ligand-gated ion channels
-GABAa receptor: a ligand-gated Cl- channel
-ionotropic glutamate receptor: a cation channel
-5-HT3 receptor: a ligand-gated cation channel
common functions of ligand-gated ion channels
1. cation channels - influx of positive ions: Na+ --> depolarisation - cell activation
2. anion channels - influx of negative ions: Cl- --> hyperpolarisation - inhibition of the cell
3. receptors found in fast responding cells - nerves and muscles
what is tubocurarine?
competitive reversible antagonist of ACh at nicotinic receptors
what is tubocurarine used for?
to relax skeletal muscle in surgery
how are the effects of tubocurarine reversed?
by increasing ACh concentration through inhibition of the enzyme acetylcholinesterase
what does GABAa receptor do?
it opens a Cl- ion channel leading to hyperpolarisation and cell inhibition
what are the GABAa receptors used for?
drugs activating the GABAa receptor, e.g. diazepam, are used as tranquillisers and anticonvulsants
what are the G-protein receptors (GPCRs) involved in?
in all types of stimulus-response pathway including hormones, neurotransmitters, sensory stimuli, etc.
what are GPCRs?
integral membrane proteins that possess seven transmembrane domains - 7TM receptors
how are the extracellular parts of GPCRs?
are often glycosylated
what do GPCRs contain?
two highly conserved cysteine residues in extracellular loops that form an intramolecular disulphide bond to stabilise the receptor structure
how do GPCRs work?
1. receptor agonist binds to GPCR
2. forms G-protein attached to membrane
3. effector gives a response
what are G-proteins consisted of?
3 subunits: alpha, beta and gamma
what do the G-protein subunit determine?
which targets are activated - the alpha subunit and beta-gamma complex can each activate intracellular targets
what are the physiological roles of GPCRs?
3. immune system and inflammation
6. autonomic nervous system
what does the sensational role of GPCRs consist of?
GPCRs respond to light (opsins), taste and smell (olfactory receptors)
what does the behavioural role of GPCRs consist of?
GPCRs in brain bind several neurotransmitters, ex serotonin and dopamine
what does the immune role of GPCRs consist of?
chemokine GPCRs meidate recruitment of immune cells to their needed location; while histamine receptors generate immune responses
what does the metabolic role of GPCRs consist of?
GPCRs in the pancreas respond to gut hormones or dietary components in order to regulate insulin and glucagon secretion
what does the autonomic nervous system role consist of?
both the sympathetic (adrenoceptors) and parasympathetic (muscarinic receptors) nervous systems use GPCRs to mediate their effects