Signalling pathways/molecules Flashcards
What is physiology?
Energy interacting with matter in living systems
Normal function of living organisms and their parts
What is the aim of all living systems?
To maximise dynamic order through regulating flow (requires energy).
(Minimise disorder - entropy)
What governs flow at the cellular level?
Specific temperature range
Molecular/ion type
Ph range
Substrates
What is pharmacology?
Study of the effect of molecules on physiological and biochemical activity of cells up through to the level of the person
What are endogenous signalling molecules?
Produced inside the body
What are exogenous signalling molecules?
Made outside the body. May be:
- plant based (natural) e.g. Morphine, antibiotics, aspirin
- synthetic (man made) - many
What is homeostasis?
Maintaining the optimal environment for cells to function
What is the sequence of negative feedback?
Imbalance - sensor - set point comparator - controller - effector - correction signal
What is a synergistic feedback loop?
Signals work together to amplify the result
E.g. Temperature control mechanisms work together to reduce/increase temperature
What is an antagonistic feedback loop?
Often called “push-pull” - where the increasing activity of one effector is accompanied by decreasing activity of an antagonistic effector
E.g. Glucagon and insulin
Adrenaline signal
What is normal body temperature?
Set point 37 degrees (+/- 1 degree)
What is the controller of temperature regulation in the body?
Hypothalamus - temperature centre - drives heat loss/gain response
What is responsible for detecting changes in temperature?
Peripheral temperature sensors in the skin e.g. TRP M8 cold receptor and TRP V4/V3 warm receptors
What are some features of the heat response?
Peripheral vessels dilate
Sweat glands activated
What are some of the mechanisms for the heat loss response?
Vasoconstriction (peripheral vessels constrict)
Muscles produce heat by shivering
thyroid gland releases hormones to increase metabolism - increases energy and heat production.
What temperature is considered hypothermia?
Less than 35 degrees
At what temperature is thermoregulation lost?
Above ~ 42 degrees
What are endocrine signalling molecules?
Produced by ductless glands
Secrete hormones into the bloodstream
Typically act over long distances
What is the potency of hormones?
Highly potent (picomolar 10^-12 M to nanomolar 10^-9 M)
What are the three major types of hormone?
Amine
Peptide/protein
Steroid
What are amine hormones?
Amino acid derivatives - small charges, hydrophilic
Receptor in the plasma membrane, caused change in membrane potential which triggers synthesis of cytosolic second messengers
Plasma half life - seconds
Give examples of amine hormones
Adrenaline
Noradrenaline
Thyroxine
What are peptide hormones?
Can be short chain - very long (200+aa), hydrophilic.
Receptor in plasma membrane, triggers synthesis of cytosolic second messengers and protein kinase activity
Plasma half life - minutes
Give examples of peptide hormone
Insulin
Glucagon
ANP/BNP
What are steroid hormones?
Derived from cholesterol - lipophilic (hydrophobic)
Intracellular receptors (cytosolic or nuclear), receptor-hormone complex controls transcription and stability of mRNA
Plasma half life - hours
Give examples of steroid hormone
Testosterone
Progesterone
Oestrogen
What is paracrine signalling?
Signalling to adjacent cells (short distance)
The synapse is an example of paracrine signalling. Discuss the signalling molecules.
Neurotransmitters
Tight coupling of signalling molecule transmission, one direction. Electrochemical to chemical signal conversion.
Very fast - msecs
What are the three major types of neurotransmitters?
Amino acids
Monoamines
Peptides
Give examples of monoamine neurotransmitters
Adrenaline - excitatory
Noradrenaline - excitatory
Dopamine - excitatory and inhibitory
Serotonin - excitatory
Give examples of amino acid neurotransmitters
Glutamate - excitatory
Glycine - mainly inhibitory
GABA - inhibitory
Give examples of peptide neurotransmitters
Opioid peptides
What is a notable exception to the major groupings of neurotransmitters
Acetyl Choline - excitatory
Paracrine signalling molecules also include local chemical mediators such as…
Interleukins
Chemokines
Interferons
Cytokines
What is autocrine signalling?
Cells respond to signalling molecules they produce/release themselves
What is a receptor?
Any molecule for which there is an interaction which has a known/putative physiological or therapeutic effect
What are the main signalling molecule targets?
R - receptors
I - ion channels
T - transporters
E - enzymes
What are important exceptions to the RITE signalling molecule targets?
Chemotherapy a target is structural protein/DNA
Antibiotics - selectively targets bacteria (another organism)
What are the four main groups of receptors?
K - kinase linked receptor e.g. Cytokine receptors
I - ion channels (ligand gated) e.g nicotinic Ach receptors
N - nuclear/intracellular e.g oestrogen receptors
G - gpcr e.g. Muscularinic Ach receptors
What are kinase linked receptors?
Wide variety of ligands (hormones, growth factors, cytokines)
Act via phosphorylation of serine/threonine/tyrosine and starts a signalling cascade
What are ligand gated ion channels?
Also called ionotropic receptors
When ligand binds, conformational change causes opening/closing of ion channel.
May be very fast e.g. Neurotransmitters
What are nuclear/intracellular receptors?
For lipid soluble ligands such as steroids
When ligand-receptor complex migrates to nucleus, binds to transcription factor, activates/inactivated a gene or set of genes
What is the function of ion channels?
Selectively allow ions (Na, K, Ca, Cl) to cross plasma membrane down electrochemical gradient
Also regulate voltage signals in excitable cells - maintain membrane potential
What are transporters/carriers?
Act in facilitated diffusion - transport ions/small molecules into/out of cells
May use ATP (against gradient) or preexisting ion gradient (symport and antiport)
During exercise heart and lung function changes to meet demand in what ways?
Supply more oxygen from lungs to muscles
And more glucose to muscle
Remove CO2 and h2o from respiration in muscle (to lungs)
Increase rate of heat loss (via capillary heat exchange network)
What Happens to proteins above 40 degrees?
Loss of structure - braking of covalent and electrostatic forces
What things might you do in practice to deal with hyperthermia?
Remove layers
Open windows
Paracetamol
Increase fluids
What things might you do in practice to deal with hypothermia?
Add layers
Bear hugger blankets
IV fluids
Why might elderly people be more susceptible to hypothermia?
Natural degeneration of muscle/fat body mass - less able to generate heat, poorer thermoregulation
May also be diabetic - diabetic neuropathy causing less response to cold sensation
Socially - poorer diet, less movement, no heating in home
