F6 Receptors and signalling Flashcards
examples of chemical messengers
- hormones
- growth factors
- neurotransmitters
- paracrine agents
simply describe hormones. site of secretion and effects
- secreted from site of synthesis in circulating blood (for long range communication)
- has short and long term effects
effect of growth factors
long term control of cell growth and differentiation
effect of neurotransmitters
fast chemical transmission at neuronal synapses
effect of paracrine agents
local control of cell behaviour in the immediate environment
explain relationship between adrenaline and noradrenaline
- adrenaline is a hormone and noradrenaline is neurotransmitter
- they work on the same set of adrenoceptors
common characteristics of receptors
- selective binding site for native hormone / transmitter
- act as molecular switches (inactive and active states)
- signal is amplified
common types of signal amplification
- second messenger (many molecules produced eg. cAMP)
- enzyme activity (catalytic: many molecules of substrate converted)
what are the 4 superfamilies of receptors?
- ligand-gated ion channels
- G protein coupled receptors
- catalytic receptors
- nuclear receptors
order the 4 types of receptors from fast to slow
- ligand-gated ion channels
- G protein coupled receptors
- catalytic receptors
- nuclear receptors
what are ligand-gated ion channels primarily responsible for?
- fast synaptic transmission
- eg. nicotinic receptors
describe signal amplification in terms of ligand-gated ion channels
- opening a single ion channel lets thousands of ions flow through
describe amplification in terms of G protein coupled receptors
- 1 receptor can activate many G proteins
- activated ‘effector’ proteins are often enzymes or ion channels
describe catalytic receptors and what happens when activated. give an example
- what are they activated by and what do they cause?
- activated by hormone binding
- causes enzyme activity
- Tyrosine Kinase receptors for growth factors eg. EGF
give an example of a nuclear receptor
- transcription factors
- eg. steroid hormones (oestrogen receptor (ER))
describe the process of transcription factor action
- ligands diffuse across membranes to intracellular receptors
- when receptors (transcription factors) are activated, they can translocate to the nucleus and bind to DNA to promote transcription
why can ligands diffuse across membranes to activate transcription factors?
they are lipophilic
how does the G protein coupled receptor system cause amplification?
- one receptor can activate many G proteins
- activated ‘effector’ proteins are often enzymes or ion channels
why does the G protein coupled receptor system have flexibility?
it’s a 3 stage system that offers variety in messengers recognised and cellular responses generated
what do GPCRs look like?
- 7 transmembrane domain helices
- 7 transmembrane receptors
- extracellular N terminus
- intercellular C terminus
- 3 extracellular loops (ECL), 3 intracellular loops (ICL)
how do GPCRs exhibit a wide diversity?
- 800 different GPCR proteins
- 7 transmembrane domain ‘template’ allows many types of binding site (receptors can be adapted for different binding sites)
NA action on arterioles in GIT (binding site and result)
- bind to alpha 1 adrenoceptor
- cause contraction
NA action on arterioles in skeletal muscle
- bind to beta 2 adrenoceptor
- cause relaxation
NA action on airway smooth muscle in bronchioles (binding site and result)
- bind to beta 2 adrenoceptor
- cause relaxation
what are the 3 main types of G protein?
Gs, Gi, Gq
(a particular receptor will normally activate just one type of G protein)
name 2 effectors of G proteins
- adenylyl cyclase
- phospholipase C (PL C)
what G proteins are adenylyl cyclase regulated by?
- regulated by Gs, Gi
- catalyses production of cAMP
what can phospholipase C be activated by?
- Gq receptor
what subunits are there of G proteins?
G alpha and G beta
what do the G alpha subunits bind to?
- binds guanine nucleotides (GDP/GTP)
- part of the activation process
what is cAMP synthesised by?
adenylyl cyclase
what does cAMP trigger and how?
- cellular responses
- bind and activate protein kinase A (PK A)
after being triggered by cAMP, what does PK A do?
- phosphorylates target proteins to change their function
what is a ‘kinase’?
phosphorylates proteins to change their function
what do Gs-coupled receptors do to adenylyl cyclase? describe the events that this allows for afterwards
- stimulate adenylyl cyclase
- adenylyl cyclase can then make cAMP from ATP
- cAMP activates PK A which activates target protein
what do Gi-coupled receptors do to adenylyl cyclase? describe the events afterwards
- inhibit adenylyl cyclase
- cAMP levels and PK A activity decreases
what do Gq-coupled receptors do?
- activate a membrane enzyme (phospholipase C / PL C)
after activation by Gq-coupled receptors, what does phospholipase C (PL C) do?
- hydrolyses a plasma membrane lipid (PIP2)
- 2 intracellular messengers are produced (IP3 and DAG)
after hydrolysis of PIP2, what does one of the products, IP3, do?
- activates ion channels and calcium ions influx into the cytoplasm resulting in smooth muscle contraction
describe the alpha 1 adrenoceptor in terms of G protein coupling and its effects
- Gq coupled
- increases intracellular calcium ions
describe the alpha 2 adrenoceptor in terms of G protein coupling and its effects
- Gi coupled
- decreases intracellular cAMP
describe the beta adrenoceptors in terms of G protein coupling and their effects
- Gs coupled
- increases intracellular cAMP
effect of noradrenaline on the arterioles in the GIT in terms of the receptor (type of GPCR and result) and response of smooth muscle
- alpha 1 adrenoceptor
- Gq coupled
- increases intracellular calcium ions
- contraction
effect of noradrenaline on the arterioles in the skeletal muscle in terms of the receptor and response in smooth muscle
- beta 2 adrenoceptor
- Gs coupled
- increases intracellular cAMP
- relaxation
effect of noradrenaline on the airway in terms of the receptor and response in smooth muscle
- beta 2 adrenoceptor
- Gs coupled
- increases intracellular cAMP
- relaxation
second messengers of Gq-coupled GPCR
- increased IP3
- DAG
- intracellular calcium ions
second messengers of Gs-coupled GPCR
- increased cAMP
second messengers of Gi-coupled GPCR
decreased cAMP
effect of Gq-coupled receptors on neurons, smooth muscle, epithelial cells and endocrine cells
- neurons: increased NT release
- smooth muscle: contraction
- epithelial cells: increased fluid secretion
- endocrine cells: increased hormone secretion
effect of Gs-coupled receptors on neurons, smooth muscle, epithelial cells and endocrine cells
- neurons: increased NT release
- smooth muscle: relaxation
- epithelial cells: increased fluid secretion
- endocrine cells: increased hormone secretion
effect of Gi-coupled receptors on neurons, smooth muscle, epithelial cells and endocrine cells
- neurons: decreased NT release
- smooth muscle: contraction
- epithelial cells: decreased fluid secretion
- secretory cells: decreased hormone secretion
what are the 4 main receptor superfamilies?
- ligand-gated ion channels
- GPCRs
- catalytic receptors
- nuclear receptors
