Lecture 10.5 - Signalling Molecules And Drug Targets Flashcards
What does ordered physiological flow require?
Energy
What are the 2 types of signalling molecules?
Endogenous
Exogenous
What are the 3 types of classification of signalling molecules?
Endogenous
Exogenous I
Exogenous II
What is meant by an Endogenous signalling molecule?
Made within the body
What is meant by an Exogenous I signalling molecule?
Natural/plant based signalling molecule (not made in the body)
What is meant by an Exogenous II signalling molecule?
Synthetic/man made
What are the 3 ways by which signalling molecules act?
Endocrine
Paracrine
Autocrine
What is the importance of extracellular signalling molecules?
Allows separate parts of the body to work in synchrony
What are the tissues called which produce endocrine hormones/signalling molecules?
Glands
How do Endocrine signalling molecules act?
Travel over long distance in the body
Act on cells that have the specific receptors
What are some important body functions that are regulated by endocrine signalling molecules?
Digestion
Metabolism/respiration
Growth - Development
Behaviours
What is mean by a signalling molecule being highly potent?
Have a strong affect when in low concentration
Why is tight feedback control important in endocrine signalling?
Synthesis and degradation of hormones well controlled to ensure processes are well regulated
What are amines?
Amino acid derivatives
What are the 3 main types of Endocrine signalling molecules (Hormones)?
Amines (Catecholamines)
Peptides/proteins
Steroids
What is the solubility of Catecholamines?
Where are their receptors?
Hydrophilic
Plasma membrane receptors
What is the solubility of Peptides and Proteins?
Where are their receptors?
Hydrophilic
Plasma membrane receptors
What is the solubility of Steroids?
Where are their receptors?
Lipophilic/hydrophobic
Nuclear or cytosolic
What molecule are all steroids derived from?
Cholesterol
What is the time course of action for Catecholamines?
milliseconds to seconds
What is the time course of action for peptides and proteins?
Mins to hours
What is the time course of action for steroids?
Hrs to days
How do steroid hormones usually act?
Receptor hormone complex controls transcription/stability of mRNAs
How do Catecholamine hormones usually act?
Change membrane potential or
Triggers second messengers
How do peptide and protein hormones usually act?
Triggers second messengers
or
Triggers protein kinase activity
How do Paracrine signalling molecules act? (Extracellular signalling)
Signalling coupled from cell to cell near to each other
What sort of extracellular signalling molecule are neurotransmitters?
Paracrine signalling molecules
How do neurotransmitters have an electrochemical action?
Chemical signal released from presynaptic membrane converts/stimulates electrical signal in post synaptic membrane
What is an excitatory synapse?
Signal at presynaptic membrane stimulates an increase in firing rate post synaptically
What is an inhibitory synapse?
Signal at presynaptic membrane decreases firing rate post synaptically
What is a specific type of “Drug target” called?
Receptor
What happens when a signalling molecule binds to its target receptor?
Bring about a change
(Could be changing a chemical/electrochemical signal)
Are endogenous signalling molecules normally agonists or antagonists?
Mainly agonists
How are exogenous signalling molecules different to endogenous signalling molecules?
Not made in the body
So the fit to receptors is not as optimal
What is meant by exogenous signalling molecules act as Antagonists and Partial agonists?
Block or reduce/attenuate biological signal
The majority of drug targets/signalling molecule targets can be remembered with what pneumonic?
RITE
What does the pneumonic RITE for signalling molecule/drug targets stand for?
R - Receptors
I - Ion Channels (Voltage gated)
T - Transporters
E - Enzymes
In chemotherapy, what is the target for the drugs?
Structural protein or DNA
What are the 4 types of Receptors that can be targeted by drugs?
Kinase linked receptors
Ion Channels (Ligand gated)
Nuclear/Intracellular
G-Protein Coupled receptors
What is the acronym that can be used to remember the 4 different types of receptors that can be targeted by drugs?
KING
Kinase linked receptors
Ion Channels (Ligand gated)
Nuclear/Intracellular
G-Protein Coupled receptors
How kinase linked receptors work?
Ligand binds
Receptor self Phosphorylates
Triggers a further cascade affecting gene transcription/protein synthesis causing specific cellular effects
How to ligand gated ion channels work?
Conformational change occurs once ligands bind
Ions can flow through causing hyperpolarisation or depolarisation
How do nuclear receptors work?
Steroids move through to the receptor complex (can be ini the nucelus)
Affects gene transcription and so protein synthesis
How do G-protein coupled receptors work?
Once bound activates G protein which will either bind to ion channel opening it
or trigger a second messenger cascade
How doo voltage gated ion channels allow movement of channels?
Enable selective flow down its electrochemical gradient
What is the difference between ligand gated ion channels and voltage gated ion channels?
Ligand gated ion channels = receptors
Voltage gated ion channels = ion channels
What are voltage gated Na+/Ca2+ channel blockers used to treat?
Epilepsy, chronic pain and migraine
How do GABA Cl- channels work?
GABA binds to chloride channel
Cl- comes in and causes hyperpolarisation
What do transport/carrier proteins do?
Transport ions or small molecules
What are the methods of transport that transporters or carriers use?
Facilitated diffusion
1º active transport (Directly use ATP against gradient)
2º uses pre-existing electrochemical gradient set up by a Na+/K+ ATPase
What are the ways drugs can affect enzymes?
Bind to active site or bind to Allosteric site
Prevent their production
The acronym king refers to the types of receptors What does the L stand for in KLING?
It is a reminder that the Ion channel is Ligand gated
