Pharmacology Flashcards
signalling molecules
- Also known as chemical messengers
- Proteins, e.g., insulin
- Peptides, e.g., glucagon, growth hormone
- Sugars
- Lipid-derived molecules
- Hormones
- Cytokines
- Neurotransmitters
- Pheromones
- Gaseous molecules (NO, H2S)
Chemical signals:
- Synthesis and release of the signalling molecule
- Transport of the signalling molecular to the target cell
- Detection of the signal by a specific receptor.
- A change in cellular behaviour triggered by activation of the receptor (activated by intracellular signalling)
- Removal of the signal, which often terminate the cellular response. In some cases this may be removal of the receptor.
Agonists vs antagonists
agonist-> bind to and activate receptors.
antagonist -> bind to and inactivate receptors.
different types of transmembrane/cell surface receptors
- GPCRs
- Ion channel linked
- Enzyme linked
GPCRs
mindmap
different kinds of intercellular signalling
- endocrine: long distance slow communication through the blood and only certain cells respond as its receptor dependent
- juxtacrine: cells with direct contact can form gap junctions and signal
- paracrine: signal to neighbouring molecules
- autocrine: molecules that can respond to its own signals
- neuronal: nerve endings respond to signals
What happens after receptor activation?
- Receptor activation leads to intracellular signalling cascades and second messenger systems
- These lead to changes in cell function
- Signals are turned off, e.g.,
-Chemical signals are enzymatically degraded.
-G proteins become inactivated by GTPases.
Cells return to previous state (unless more signal is around).
The three stages of Intra cell communication:
- Reception
- A chemical message binds to a protein on the cell surface.
2. Transduction: - The binding of the signal molecule alters the receptor
- This starts a cascade of reactions.
3. Response: - The transduction pathway triggers a response
- The responses can vary from turning on a gene, activating an enzyme, rearranging the cytoskeleton.
- A chemical message binds to a protein on the cell surface.
how is signalling controlled
• By post translational modification, e.g., phosphorylation
• By regulating whether a G protein has bound GDP or GTP
By provision of activators such as Ca2+ and cAMP.
protein phosphorylation
• Kinase is an enzyme that phosphorylates proteins.
• Kinase add a phosphate group
• Most common amino acids:
-Serine -Threonine -Tyrosine
* Phosphatase is an enzyme that dephosphorylates proteins. * Phosphatases remove the phosphate group.
Serine/Threonine kinases:
• Ca2+/calmodulin-dependent protein kinases or CaM kinases.
• Protein Kinase A (PKA)
• Protein Kinase C (PKC)
• Mitogen-activated protein kinases (MAPK)
Tyrosine kinases:
• Non receptor tyrosine kinases e.g., Src family kinases- knowledge of these kinases has been fundamental to our understanding of cancer.
Receptor tyrosine kinases (RTKs) e.g., Epidermal growth factor receptor (EGFR)
ion channels
-five transmemembrane subunits come together to form a channel
-transports Na+, K+, Ca2+, Cl- ions along an electrochemical gradient.
-opens in response to changes in transmembrane potential: voltage gated ion channels
-opens in respond to changes in chemicals: ligand gates ion channels/ionotropic receptors
-once activates, allows ions to move through.
E.g., Nicotinic (acetylcholine receptor), GABA receptor, glycine receptor, 5-HT3 receptor, etc.
Second messenger systems
concentration changes in response to receptor activation by agonist:
AC -> cAMP
PLC -> InsP3/DAG
GC -> cGMP
Enzyme linked receptors:
- single membrane spanning domain
- cytoplasmic enzymes that induce signalling are normally protein tyrosine kinases.
- extracellular ligand binding domain, a single transmembrane helix, a cytoplasmic region containing the protein tyrosine kinase activity
Receptor Tyrosine kinases: ligand binding activates enzyme activity within the cytoplasmic domain.
- the respond usually required receptor dimerisation.
- tyrosine residues in the intracellular domains are auto-phosphorylated in respond to the signal
- typically, responses are slow
Cytoplasmic/Nuclear
- For signals that can cross the cell membrane
- Huge family of receptors
- Examples include oestrogen, thyroid, retinoic acid, and steroid hormone receptors.
- Alter gene transcription (and hence protein levels) directly.
Administration of drugs
- Oral
- Injection: IV, IM, SC
- I halation
- Sunlingual or buccal
- Rectal
- Other epithelial surfaces (skin, cornea, vaginal, nasal mucosa)
