Muscle activity involves biochemical reactions that produce heat due to ________ being converted to ____________
Apart from conversion of ATP to ADP, heat is also generated by what?
Movement of muscle contractile proteins
What are the main extracellular signalling groups?
Endocrine signalling involves which class of molecule?
What are the major types of endocrine signalling molecules/hormones?
Hydrophilic 1 - Amines (Chatecholamines) e.g. Noradrenaline
Hydrophilic 2 - Peptides to proteins e.g. Insulin
Lipophilic- Steroids e.g. Testosterone
What are the time courses of action of amines, proteins and steroids?
Amines: milliseconds - seconds
Proteins: minutes- hours
Steroids: hours- days
Where are the receptors for each of these type of extracellular signalling molecule?
Amines- within the plasma membrane
Proteins- within the plasma membrane
Steroids- Intracellularly, within the cytosol or nucleus
What is the plasma half life of:
2) Peptides to proteins
What do exogenous analogous signalling molecules do?
They attempt to mimic endogenous signalling molecules
Give two examples of exogenous endocrine analogues and what they might be used for.
Adrenaline- administered IV in emergency situations
Insulin- allows adequate control of blood sugar in diabetic patients
What is paracrine signalling?
Signalling from one cell which induces change in nearby cells
Are paracrine signalling molecules are released intra- or extracellularly?
Signalling molecules that signal from neurone to neurone are known as what?
Multiple synapsing of the CNS allows what?
Parallel processing of information
Transmission velocity of neurotransmitters is measured in what?
What common neurotransmitter is excitatory at the end organ?
Give 4 examples of monoamine neurotransmitters? State whether they are stimulatory or inhibitory.
Adrenaline - stimulatory
Noradrenaline - stimulatory
Dopamine - stimulatory and inhibitory
Give three examples of amino acids that act as neurotransmitters? State whether they are excitatory or inhibitory.
Glycine- Mostly inhibitory
Local chemical meditators can also be examples of _________ signalling molecules
Some local chemical mediators can be classified as ____________ and ___________
Give four examples of cytokines
Give two examples of Eicosanoids
Besides Cytokines and Eicosanoids name four other local chemical mediators
Platelet Activating Factor
When would local chemical mediators be released?
Following local injury
What are the advantages of eliciting a local response?
It is rapid, focused and integrated and does not need to involve the whole body resource
Give three examples of the therapeutic application of paracrine signalling molecules of the neurotransmitter variety
Dopamine precursors and agents- inhibit dopamine breakdown in Parkinsonism
Fluoxetine- SSRIs to slow the reuptake of Serotonin in the CNA in depression
GABA receptor modulators/reducers of GABA synthesis- In epilepsy
Therapeutic paracrine signalling molecules that act as local chemical mediators can be used to treat what?
Moderate pain (NSAIDs)
What is autocrine signalling?
When cells respond to signalling molecules that they produce and release themselves
Autocrine signalling shares many signalling molecules what what other signalling type? Such as?
Such as cytokines and growth factors
Autocrine signalling molecules typically act over what distances when released from the cell?
Endogenous and exogenous signalling molecules bring about a __________ in functional status
The signal produced when a signalling molecule binds its target can function to _______ the original signal to produce another signal, and ultimately perform a specific task e.g. _______ or ________
Endogenous signalling molecules have been engineered by ____________ and therefore carry out their function optimally
Exogenous signalling molecules are often engineered by _________ _________ to carry and transfer their ‘imposter’ signal. The signal is still carried, but the _____ may be sub-optimal.
Exogenous signalling molecules may produce unwanted _____________.
Name 4 classes of targets for signalling molecules
Name the 4 types of RECEPTORS that signalling molecules may act on
Ion channels (Ligand Gated!!)
G Protein Couple Receptors (GPCRs)
Name the three types of ion channels
Kinase-linked receptors have a timescale of what?
Kinase-linked receptors bind ligands such as?
How do kinase-linked receptors work?
Via phosphorylation of specific groups which activates a SIGNALLING CASCADE leading to gene transcription e.g. growth/differentiation
Ligand gated ion channels are a type of receptor. What are these receptors also known as? What does this mean?
They form an ion channel pore
What is the time scale of ligand gated ion channels?
Ligand gated ion channels gate the flow of _____ across the plasma membrane for the duration of ________
Give some examples of ligands that may bind to a ligand-gated ion channel
Neurotransmitters such as: Acetyl Choline (ACh), GABA and NMDA
Ligand gated ion channels allow _____ currents and _________ change which can drive or modulate action potential generation in ________ and ________ in muscle
Nuclear/ Intracellular receptors have a time scale of what?
In order to bind to a nuclear/ intracellular receptor, ligands need to be what?
Once the ligand is bound, what happens at the nuclear receptor?
The ligand-receptor complex migrates to the nucleus, if it is not already there, and binds to a TRANSCRIPTION FACTOR
Once the ligand-receptor complex is bound to a transcription factor, what happens?
A set of genes are activated or inactivated
Apart from steroids, what other ligands can bind to nuclear/intracellular receptors?
Thyroid hormone, Vitamin D, Xenobiotics
GPCRs are also known as what type of receptor?
What does this mean?
It is a membrane receptor that acts through secondary messengers
What are the largest family of receptors?
Give two examples of groups of molecules that can bind to GPCRs
What is the time scale of GPCRs?
Give two examples of GPCRs that have ligands that are neurotransmitters
Musclarinic acetyl choline (ACh) receptor (serotonin) and adrenoceptors (dopamine)
What are the three major types of GPCR?
Gq, Gi and Gs
What is the difference between ionotropic and metabotropic receptors
Ionotropic: form an ion channel pore in the cell membrane
Metabotropic: acts by signal transduction through a secondary messenger
Ion channels are another target of cell signalling molecule. How do they work?
By selectively allowing ion current to flow across the plasma membrane
Name 4 major ion currents
Na+ (Sodium ions)
K+ (Potassium ions)
Ca2+ (Calcium ions)
Cl- (Chloride ions)
Ion channels regulate voltage signals in excitable cells to maintain _________________
True of false: Ion channels are selective
Voltage- gated ion channels (VGICs) primary activity is dependent on change in ______ ______ density
Ion channel activity can be facilitated or inhibited by ___________ of intracellular sits on channels via GPCR Protein Kinase A and Protein Kinase C activation
Activity of ion channels can be allosterically modulated by endogenous intracellular signalling molecules such as ______, _______ and Ca2+ signalling proteins e.g. _____________
Transporters/Carriers in the plasma membrane do what via which methods of movement?
Transport ions or small molecules using FACILITATED DIFFUSION or ACTIVE TRANSPORT
With regard to movement of molecules, what features will determine whether movement is achieved by facilitated diffusion or active transport?
The concentration gradient (against a gradient=active transport)
The size of the molecule (large= active transport)
The polarity of the molecule (polar molecules= active transport)
What energy sources are required to achieve active transport?
ATP or a pre-existing ion gradient (in symport/antiport)
Which transporters are responsible for the efflux of drugs and imposter molecules from cells?
Multi-drug Resistance Proteins (MDRPs)
Part of the ATP-binding cassette ABC superfamily
An important example of transport in the body is in neurotransmitter re-uptake. Give three examples of neurotransmitters that would be taken back up in this way.
Co-transport of _____ can be used to drive transport. This type of transport is known as _________.
Na+ (Sodium ions)
List 3 common uses of enzymes
Give an example of competitive inhibition at active binding site by a drug.
Aspirin binding to COX enzyme