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What is physiology?
the study of function of the body - how the body parts work and carry out their life sustaining activities
How is a constant steady state of internal environment achieved?
Homeostasis
What is intracellular fluid?
fluid inside the cell
What is extracellular fluid?
fluid outside the cell (blood plasma and interstitial fluid)
What is the major cation and anion in ECF?
Sodium cation and Chloride is anion
What is the major cation in ICF?
Potassium
What is transcellular fluid?
Fluid consisting of cerebrospinal, pleural, peritoneal and synovial fluids., secreted by epithelial cels and found in joints.
What are the components of a feedback mechanism?
Stimulus, receptors, CNS, effectors
What is negative feedback?
A response to a change in the body that counteracts or opposes the initial change.
What is positive feedback?
Feedback that increases the output of a process.
What did Langley's experiment with pilocarpine and atropine do?
Gave rise to the idea of receptors.
What is the effect of pilocarpine on heart rate and saliva production?
Pilocarpine slows heart rate and increases saliva production.
What do atropine do to pilocarpine?
Atropine blocks the actions of pilocarpine, as it is an antagonist.
What did Langley do with chicken leg muscles, nicotine and curare?
Electrical stimulation caused contraction of muscle
Application of nicotine to muscle also caused contraction
Found that nicotine mimics electrical stimulation
When curare applied to muscle, antagonised effects of electrical and nicotine stimulation
What happened when Langley cut back the nerves of the chicken leg muscles?
applying nicotine to nerves caused contraction
stimulating nerves produces substances that mimics action of nicotine
What did Ehrlich's experiment with blood cells show?
Treated blood cells with different dyes
Different cell took up different dyes
Showed specificity of interaction between molecule and receptor
What are receptors?
Recognition sites for cell mediators (neurotransmitters/hormones), bind to molecules to modulate activity of cells.
What are cell mediators?
Extracellular signal molecules
What is cell signalling?
Where a receptor detects extracellular signal to generate intracellular signal(s).
What is signal transduction?
Process of converting extracellular signals into intracellular signals.
What is endocrine signalling?
Mediator (i.e. hormone) is secreted into the blood and transported around the body(long distance) to act on multiple receptors
What is paracrine signalling?
signalling molecules act locally (short distance), effecting neighbouring cells
What is neuronal signalling?
release of neurotransmitters to act on a target cell
Long distance
Fast acting
Specific
Synapses form between neurones and target
What is contact dependent signalling?
signalling molecules are expressed on the cell surface of one cell and bind to the receptors of another cell when the two come into contact.
What are some examples of endocrine signalling?
Adrenaline
Insulin
What are some examples of paracrine signalling?
Histamine
Nitrous oxide
Lipid mediators
What are some examples drugs effecting neuronal signalling?
synapses restricts signal between neurone and target
drugs influence neurotransmitter synthesis
Drugs interfere with storage, leading to depletion
Drugs prevent neurotransmitter release
Drugs interfere with receptors
What are some examples of contact dependent signalling?
used in immune system ( T cells receptors detect antigen presenting cells and activate to recognised infected/damaged cells)
Car-T immunotherapy (T cells activated to recognise and kill cancer tumour cells)
What are bioassays and what are they used for?
experimental assays where concentration/potency of a substance is measured by its produced biological response.
can be used for
Measure pharmacological activity of new drug
Investigate function of endogenous mediators
Measure drug toxicity/side effects
What did Otto Loewi discover and how?
Discovered chemical transmission between neurotransmitters by showing the effect of acetylcholine as an endogenous neurotransmitter, using a frog heart.
What did Henry Dale do?
Later showed acetylcholine was used as a neurotransmitter at NMJ and autonomic ganglia.
What was Henry Dale's experiment?
Used bioassays with dorsal muscle of leeches to measure acetylcholine release following stimulation of different preparations
What did Henry Dale's experiment show?
showed neurones were defined by the neurotransmitter they synthesised/used
Defined neurotransmitters as 'cholinergic', 'adrenergic' or 'gabaergic'
What is the experimental criteria for a substance to be a mediator?
For a substance to be a mediator:
Must be released in sufficient amounts to produce biological action on target cells within appropriate time
Application of sample of mediator produces original biological effect
Interference with synthesis, release or action ablates/modulates original response
What is the production of mediators dependent on?
Depends on enzymes and active genes
cells can produce more than one kind of mediator
Some secretory vesicles store more than one type of transmitter
What are the two types of chemical mediators?
1.) Preformed and stored in specialised vesicles and released by exocytosis (allows for rapid communication)
2.) Mediator produced on demand, released by diffusion or constitutive secretion (takes longer to act)
What happens when neurons are stimulated?
Action potential generated
Acetylcholine released
What do vesicles involved in regulated exocytosis have?
calcium sensor protein (synaptotagmin)
Required for efficient membrane fusion
What enzyme is involved with cholinergic synapses?
Acetylcholinesterase
What do vesicular transporters do?
Load transmitters into synaptic vesicles
What is pharmacology?
The study of mechanisms by which drugs affect function of living things.
Where are most receptors found?
majority embedded in membrane
Transmembrane domains
Extracellular domain
What are the different classifications of receptors?
Ligand-gated ion channels
G-protein coupled receptors
Kinase linked receptors
Nuclear receptors
What are ligand-gated ion channel receptors?
Binding site facing outside of cell with series of transmembrane spanning that possess ligand binding domain
Allows formation of pores
What are G-protein coupled receptors?
All proteins have 7 transmembrane domains
Binding domain depends on sub-family and binding molecules
When chemical mediator binds, G protein is activated
What are kinase-linked receptors?
Binding in membrane by single transmembrane domain
Involved in hormone and insulin signalling
Signal transduction associated with kinase (phosphorylates proteins)
Kinase can be part of receptor or attached as separate molecule to receptor protein
What are nuclear receptors?
No transmembrane domain
Found inside cytoplasm or nucleus
DNA binding motifs
Control transcription of specific genes
What is an agonist?
drug/molecule that binds to receptor to bring about a cellular response, leading to signal transduction
What is an antagonist?
Drug that inhibit response of agonist, bind to receptor but don't elicit a response
What is a ligand?
Any molecule/drug that binds to a receptor
Can be agonistic or antagonistic
Which receptors are the fastest at signal transduction?
Ligand-gated ion channels are the most rapid (ms or less) as they only require a small conformational change.
Why are G-protein, kinase-linked and nuclear receptors slower?
G-protein receptor mechanism is more complicated, receptor activates G protein that controls function of other proteins (channels/enzymes)
Kinase-linked receptors take longer due to phosphorylation, gene transcription and protein synthesis (takes hours)
Nuclear receptors require gene transcription and protein synthesis