drug receptor Flashcards
what are the 4 main receptor classes/types
- ligand gated ion channels
- g coupled protein receptor
- enzymes linked receptor/ kinase linked receptor
- nuclear receptor
what is the structure of ligand gated ion channels
- consists of 4/5 subunits making a cylinder/helical structure
- binding of ligand to the orthosteric site opens ion channel allows the flow or one or a few ions (na, k, ca or cl)
- can cause depolarisation or hyperpolarisation of membrane
what is the speed of transmission in ligand gated ion channels
milli seconds
what are three examples of ligand gated ion channels
- nicotinic cholinergic
- GABA-A
- 5HT3
what are examples of other ion channels that drugs target which are not ligand gated receptors
- voltage gate ion channels which are specific to one ion examples include
- calcium voltage gated ion channels, amlodipine (calcium channel blockers) targets these and help with angina and hypertension
- sodium voltage gated ion Chanels, amiodrone (sodium ion channel blockers) targets these and help with heart irregularities
what is the most common receptor for drug target and what percentage of drugs target these receptors
- GPCR
- 30%
- over 856 gpcr’s
what is the structure of GPCRs
- has an extracellular N terminus
- transmembrane 7 alpha helical domains
- intracellular c terminus
- associated with a G protein - intracellularly
- G proteins - made of 3 subunits an alpha, beta, gamma
what is the different types of G proteins
- Gs- activation of this G protein results in activation of adenylate cyclase this results in more cyclic AMP being produced (secondary messenger)
- Gi/o- inhibits adenylate cyclase so less cAMP
- Gq/11- stimulated phospholipase c so more IP3 and DAG (secondary messenger)
- Go- negatively regulates adenylate cyclase and positivity regulated phospholipase c
what happens when a ligand/agonist binds to GPCR
- the GTP bound to the alpha subunit is replaced by GDP
- alpha subunit separates from beta/gamma subunit
- downstream signalling molecules activated
- secondary messenger formed e.g. cAMP
- also note one gpcr can bind to more than one type of g protein and therefore more that one type of secondary messenger be formed resulting in more that one outcome/effect
what is the transmission of GPCR
- SECONDS
- Due to secondary messenger needing to be formed
what is the transmission of enzyme linked/ kinase linked receptors
hours
what is an example of a gpcr
muscarinic choligernic
how can enzyme linked receptors be divided into
- many types of enzyme linked receptors
- e.g. cytokine receptors
- tyrosine kinase linked receptors
- serine kinases
- toll like receptors
what is the structure of tyrosine kinase linked receptors
- has an extracellular ligand binding domain
- transmembrane region
- intracellular kinase domain
- single membrane
what does kinase linked receptors respond to
- respond to growth factors and indirectly regulate gene expression
what happens when agonist/ligand bind to tyrosine kinase linked receptor
- tyrosine kinase receptor dimerizes
- tyrosine residues undergo autophosphorylation
- creates binding sites for certain proteins such as Grb2
- causes phosphorylation of the protein
- activates ras and the cycle goes on - kinase cascade
what are cytokine receptors
- don’t have an intracellular kinase domain
- but are associated with a tyrosine kinase so when a ligand bind this tyrosine kinase is activated (JAK)
- bind specifically to cytokines and are often dimeric
what are some examples of tyrosine kinase receptors and the drugs which target it
- HER2 is a tyrosine kinase linked receptor and are targeted by trastuzumab which are monoclonal antibodies used to treat breast cancer
- insulin receptors are tyrosine kinase linked receptors (exist as a dimer- held by disulphide bridges)
- imatinib are cancer drugs which target tyrosine kinase linked receptors
what are the structure of nuclear receptors
- soluble protein present in cytoplasm and sometimes nucleus
- ligand activates transcription factors
- bind to DNA once activated
- usually homo or hetero dimer
- 3 domains a dna binding domain, ligand binding domain, activation function domain
what are the two types of nuclear receptors
-steroid receptors (oestrogen) which are usually found in the cytoplasm bound to a protein such as heart shock proteins
- PPARs where there’s 3 types (alpha, beta and gamma)
- alpha has roles in homeostasis, gamma has roles in insulin sensitisation, beta has roles in fatty acid metabolism
- PPARs mostly reside in nucleus
what is the transmission time for nuclear receptors
hours
what drug targets PPARy (nuclear receptors)
pioglitazone acta as an agonist for PPARy
used as a treatment for diabetes type 2
what drugs target estrogen receptors (steroid- nuclear)
ethinylestradiol
- used in contraceptive pill etc
what is another words for GPCR
metabotropic receptors
what is another word for ligand gated ion channels
- ionotropic
