F6. Receptors and signalling Flashcards
Describe hormones
-Secreted into circulating blood
-Long range communication
-Short and long term effects
Describe neurotransmitters
Fast chemical transmission
at neuronal synapses
Describe growth factors
Long term control of cell growth
and differentiation
Describe paracrine agents
Local control of cell behaviour in the immediate environment
common characteristics of receptors?
-selective binding site for native hormone/ transmitter
-act as molecular switches- inactive and active states
-signal is amplified
Describe common types of signal amplification
-first messenger e.g hormone binds to receptor
-second messenger: many molecules produced or enzyme activity: many molecules of substrate converted
what are the four types of receptors? (from fast to slow)
-ligand gated ion channels
-g protein coupled receptors
-catalytic receptors
-nuclear receptors
ONE NOTE
Describe ligand gated ion channels
-fast synaptic transmission (e.g nicotinic receptors)
-acetylcholine binds to acetylcholine receptors causing an influx of Na+ causing depolarisation
-opening a single channel lets 1000s ions flow through
Describe G protein coupled receptors
-most common receptor type in the human genome
-amplification: one receptor can activate many G proteins, activated “effector” proteins are often enzymes or ion channels
-three stage system offers variety in messengers recognised and cellular responses generated
Describe catalytic receptors
-receptor has enzyme activity activated by hormone binding
Describe tyrosine kinase receptors for growth factors e.g EGF mechanism
-Tyr phosphorylation of receptor: a kinase phosphorylates (adds phosphates to) the target protein- common in signalling
-Adaptor proteins: recognise the phosphorylated receptor and produce multiple signals, including gene expression changes
ONE NOTE
Describe nuclear receptors
-Ligands diffuse across membranes to intracellular receptors
-active receptors bind DNA and promote transcription
-amplification: many mRNA/ new proteins produced from activated transcription site
what do G protein coupled receptors (GPCRs) look like?
-7 transmembrane (7TM) receptors
-Extracellular N terminus
-Intracellular C terminus
-3 extracellular loops (ECL), 3 intracellular loops (ICL)
-Helices are arranged in a bundle
ONE NOTE
how many G coupled proteins are there in man?
-around 800 different GPCRs as 7TM “template” allows for many types of binding site
what are the different classes of messenger?
-metal ions
-amino acids
-biogenic amines
-lipids
-peptides
-protein hormones
Specific GPRCs for all these different classes of messenger
ONE NOTE
what are the 5 main GPCR adrenoceptors for adrenaline/ noradrenaline?
a1-AR, a2-AR, B1-AR, B2-AR, B3-AR
Describe receptor subtypes?
multiple receptor subtypes are common for nearly all the messengers you will meet. This is great for pharmacologists to create selective ligands (e.g salbutamol, a B2-AR agonist)
Describe adrenoreceptor control of smooth muscle
-The same messenger can affect the same cell type but produce an opposite response. This is due to multiple receptor subtypes coupled to distinct intracellular signalling pathways
Describe the flexibility in GPCR signalling
receptor subtypes can activate different G proteins and effectors
what are the three main types of G protein?
Gs, Gi, Gq
a particular receptor will normally activate just one type of G protein
what G proteins affect what effectors, producing what response?
-Gs, Gi proteins affect Adenylyl cyclase enzyme triggering cAMP
-Gq protein affects phospholipase C (PLC) enzyme triggering intracellular Ca2+
how is cAMP formed?
it is synthesised by adenylyl cyclase (membrane enzyme) from ATP
ONE NOTE
How does cAMP work as a second messenger?
-cAMP triggers cellular responses by binding and activating protein kiinase A
-PK A then phosphorylates target proteins to change their function
-altered size and charge affects protein conformation/ interactions
How does Gs coupled receptors work?
-stimulate adenylyl cyclase e.g B2-AR
How do Gi coupled receptors work?
-inhibit adenylyl cyclase e.g a2-AR
-cAMP levels and PK A activity decreased
How do Gq coupled receptors work?
-activates membrane enzyme- phospholipase C (PL C)
-PL C hydrolyses a plasma membrane lipid-phosphatidylinositol 4,5-bisphosphate (PIP2)
-Two intracellular messengers are produced: inositol 1,4,5-trisphosphate (IP3) – diffusible
and diacylglycerol (DAG) – membrane bound
-IP3 releases calcium ions (Ca2+) as another 2nd messenger
what does DAG produce?
produces signals too (protein kinase C)
Increased intracellular Ca2+ results in?
smooth muscle contraction
what is the 2nd messenger and function of Gq-coupled receptors?
second messenger: increased IP3, DAG, Intracellular Ca2+
function:
-increased neurotransmitter release, smooth muscle contraction, increased fluid secretion in epithelial cells, increased hormone secretion in endocrine cells
What is the 2nd messenger and function of Gs-coupled receptors
2nd messenger: increased cAMP
function:
-increased neurotransmitter release, smooth muscle relaxation, increased fluid secretion in epithelial cells, increased hormone secretion in endocrine cells
What is the 2nd messenger and function of Gi coupled receptors?
2nd messenger: decreased cAMP
function:
-decreased neurotransmitter release, smooth muscle contraction, decreased fluid secretion in epithelial cells, decreased hormone secretion in secretory cells
