Pharmacology- Biological Basis for Therapy (incomplete) Flashcards
What is a receptor?
sensing elements of chemical communication in the body
Receptors targets
neurotransmitters, hormones, other mediators and many therapeutic agents
chemical signalling of autocrine cells
cell signals to itself
chemical signalling of paracrine cells
cell signals to its close neighbours
chemical signalling of endocrine cells
Cell signals via molecules transported by the blood to target distant cells
Major types of receptors
- Ligand gated ion channels/ inotropic receptors
- G protein coupled receptors/ metabotropic receptors
- kinase-linked receptors/ enzyme-linked receptors
- nuclear receptors
Ligand gated ion channels/ inotropic receptors
found at plasma membrane
targeted by hydrophilic signalling molecules eg acetylcholine
act on a ms timescale
G coupled protein receptors/ metabotropic receptors
found at plasma membrane
targeted by hydrophilic signalling molecules eg
signal on a s timescale
kinase linked receptors/ enzyme linked receptors
found at plasma membrane
targeted by hydrophilic protein mediators eg insulin
work on an hr timescale
nuclear receptors
found intracellularly in the nucleus (or cytoplasm and translocate to nuclease when activated by agonist)
targeted by hydrophobic signalling molecules
very slow action on hrs/ day timescale
Ion channels
transmembrane pores formed by glycoproteins
span membrane to create ion conducting pathway for selected ions
Gating
regulatory signals that cause the channel to cycle reversibly between a closed (non-conducting) state and open (conducting)
what happens when ion channel gate is open?
conduct selected ions passively down their electrochemical gradients at incredible rates frequently mediating very rapid electrical signals (e.g. action potentials, synaptic potentials)
What are ion channels gated by?
chemical signals (LGICs)
transmembrane voltage (VGICs)
Physical stimuli (thermal/ mechanical energy)
Example of LGIC
nicotinic acetylcholine receptor of skeletal muscle and neurones
second messenger systems
most cell surface receptors signal this way
it is when receptor activation modulates the activity of an effector that is generally an enzyme, by can be an ion channel
GCPR structure
- integral membrane protein
- single polypeptide with ec NH2 and ic COOH
- contains 7 transmembrane alpha helical spans
- sometimes function as dimers
G protein
- peripheral membrane protein
- 3 polypeptide subunits
- contains a guanine nucleotide binding site in the alpha subunit that can hold guanosine triphosphate (GTP) or guanosine diphosphate (GDP)
- named according to their alpha subunit
inactive G protein
guanine nucleotide binding site of the alpha subunit is occupied by GDP
active G protein
guanine nucleotide binding site of the α-subunit is occupied by GTP and the α- and βγ-subunits separate (dissociate) from each other
How is G protein activated?
agonist binds to GPCR, causes conformational change, which is transmitted to the GP alpha sub unit
this releases GDP, allowing GTP to bind in its place (guanine nucleotide exchange)
separates from the receptors and beta gamma dimer (subunits dissociation)
generates a free GTP bound alpha subunit and beta gamma dimer
