Extracellular signalling Flashcards
Why do cells communicate together
- regulate development
- control growth & division
- co-ordinate function
What happens when cellular communication goes wrong
- signal lost (diabetes 1)
- target ignores signal (diabetes 2)
- signal doesn’t reach target (multiple sclerosis)
- too much signal (brain damage)
- multiple breakdowns (cancer)
What happens in diabetes 1
- signal (insulin) lost
- pancreatic B cells no longer synthesise
What happens in diabetes 2
- insulin ignored by defective target receptor
What happens in multiple sclerosis
- nerve impulse not reach target
- breakdown of myelin sheath surrounding neurone
What happens in brain damage
- excitetoxicity
- too much glutamate neurotransmitter
- neural degeneration
- death
What happens in cancer
- over-active
- under-active
- confused signalling
What are the three ways in which cells communicate (signal)
- remote by secreted proteins
- contact by plasma membrane-bound molecules (juxtacrine)
- contact via gap junctions
What happens in contact via gap junctions
- GJ join cytoplasm of interacting cells
- passage of signals
Give an example of gap junction
cardiomyocyte contraction (cc)
How do gap junctions in cc form
- connexin protein expressed by adjacent cells
- channel —> cytoplasmic content movement (2nd messenger)
- rapid electrical; coupling
What protein make the gap junctions in the cardiac muscle
Connexin-43
What are the stages of remote signalling
- reception
- transduction
- response
What are extracellular signal molecules referred to as
1st messenger
Give examples of 1st messenger
- growth factors
- neurotransmitters
- hormones
- cytokines
What are 1st messengers synthesised by
Signalling cells
What do 1st messengers have
- specific response in target cells
- specific receptors
What are the four types of intercellular signalling
- autocrine
- paracrine
- endocrine
- neuronal
What happens in autocrine
- cells respond to self-signals
What happens in paracrine
- signalling acting on nearby cells
What happens in endocrine
- signal released in blood
- circulate
- act on specific target
What happens in neuronal
- response to nerve impulse
- neurotransmitters released
- act on target cells
What are hormones
Chemical messengers transport signal from one cell to another
Name two types of hormones
- endocrine
- paracrine
Where are endocrine hormones released into
- blood
- by endocrine glands
Where are paracrine hormones released into
- diffuse thru intestinal tissue
What do hormones regulate
- energy needs
- protein & nucleic acid metabolism
- mineral and electrolyte metabolism
- synthesis and release of hormones
How is hormone activity regulated
- positive feedback
- negative feedback
Give examples of hydrophilic hormones
- catecholamines
- peptide hormones
Give examples of lipid-based hormones
- steroids
- thyroid hormones
- sterol hormones
Give examples of catecholamines
- adrenaline
- noradrenaline
- dopamine
- serotonin
- histamine
Give examples of peptide hormones
- insulin
- glucagon
- angiotensin II
Give examples of steroids
- oestrogen
- testosterone
- cortisol
- aldosterone
Give examples of thyroid hormones
- thyroxine (T4)
- tri-iodothyronine (T3)
Give examples of sterol hormones
- calcitrol (Vitamin D)
What has to happen to signal of extracellular in order to have an effect
- convert into intercellular signal
What are receptors and what do they do
- co-ordinate functions of cells in response to signals
- shape complementary to messenger for interaction
Give an example of receptor subtype specific
Adrenaline
- liver, muscle: glycogen degeneration
- adipose: fatty acid production
- cardiovascular: heart rate, bloop pres. up
What determines the class of a receptor
- molecular structure
- transduction mechanism
What are the two types of receptions
- cell-surface - hydrophilic
- intracellular - lipid-based
Name cell-surface membranes
- ligand-gated ion channel
- G-protein coupled
- tyrosine kinase
Name intracellular receptor
- nuclear hormone receptor
Describe ligand-gated ion channels
- ionotropic
- very fast
- synaptic transmission
Explain mechanism of ligand-gated ion channels
- binding —> conformational change
- ions flow
- cell electrical potential altered
Where are ligand-gated channels found
Where is binding site
- electrically excitable cells
- extracellular side
What is the structure of ligand-gated ion channels
4 or 5 heteromeric subunits
Central pore
Give examples of ligand-gated ion channels
- nAChR
- GABAa
- GlyR
- 5-HT3R
How does nicotine acetylcholine receptor (nAChR) work
- in. Na+ & K+ permeability
- Na+ in, K+ out
- depolarisation
What are G-protein-coupled-receptors (GPCR)
- metabotropic
- heptahelical
What is the structure of GPCR
- single polypeptide chain
- 7 a-helical regions —> intracellular & extracellular loops
- NH2 terminus
- COOH cytosolical terminus
What is a 2ry messenger
- small intracellular molecule
- formed in reception to receptor activation
What is Renin-Angiotensin system (RAS)
- feedback system
What does RAS control
- blood pressure
- blood vol.
- electrolyte homeostasis
What does RAS consist of
- renin
- angiotensin-converting enzyme (ACE)
What does renin (made in kidney) do
- cleaves a decapeptide from N-terminus from angiotensinogen (made in liver)
What is ACE
Membrane-bound dipeptidyl carboxypeptidase
What does ACE do
- cleaves C-terminal dipeptides from angiotensin
- producing angiotensin 2
What does Ang 2 do
- in. Sympathetic activity
- water retention
- aldosterone secretion
- arteriolar vasoconstriction
- in. Bp
- ADH secretion
What is the structure of Ang 2
- peptide hormone
- octapeptide
What are the receptors of Ang 2
- GPCRs
- AT1, AT2
What effect does Ang ii have if bound to AT1
- vasoconstriction
- increased NA
- Na+ reabsorption
- aldosterone secretion
- vascular growth
What effect does Ang ii have if bound to AT2
Opposite AT1
What strategies are used to control RAS against HF
- inhibit renin release/ activity
- ACE inhibitors
- AT1 receptor antagonists (losaratan)
- aldosterone receptor antagonists
What is the structure of kinase-linked receptors
- single transmembrane helix
- large extracellular domain
- intracellular catalytic domain
- large & heterogeneous
Explain catalytic receptors (kinase-linked)
- receptor is enzyme
- tyrosine kinase receptors
- activated by insulin & growth factors
Explain non-catalytic receptors (kinase-linked)
- receptor act thru cytoplasmic tyrosine kinases
- cytokines
- growth hormones
What happens after ligand binding in kinase linked receptors
- receptor dimerisation
- indirectly regulate transcription
- cell division
- tissue repair
- apoptosis
What is the structure of nuclear hormone receptors
- monomeric
- lipophilic hormones
- separate ligand ; DNA binding domains
What do nuclear hormones receptors do
- regulate gene transcription
Examples of hormones that are acted on by nuclear receptors
- steroid hormones
- thyroid hormones
How do hormones affect gene transcription in nuclear receptors
- hormones diffuse across memb.
- interact with cytosolic/nuclear receptors
- hormone-receptor complexes
- bind to DNA —> affect transcription
What do dendrites, cell bodies and axons do
- receive info.
- assimilates info.
- ends at nerve terminal
Describe neurotransmission
- action potential
- synaptic vesicles fusing synaptic memb.
- Ca2+ diff. in
- neurotransmitter (ACh) released by exocytosis
- neurotransmitter across syn cleft
- binds to post-syn cleft
- initiates response
What are neurotransmitters
Chemical messengers of nervous system
Give examples of neurotransmitters
- ACh
- monoamines
- amino acids
- peptides
- lipids
Give examples of monoamines neurotransmitters
- noradrenaline
- adrenaline
- dopamine
- histamine
- serotonin
Give examples of amino acids neurotransmitters
- glutamate
- aspartate
- glycine
- GABA
Give examples of peptides neurotransmitters
- endorphins
- substance P
- neuroticisms
- neurotensin
Give examples of lipids neurotransmitters
- anandamide
What is the life cycle of a neurotransmitter
- synthesis
- storage
- release
- receptor activation
- neurotransmitter inactivation
What are the two types of depression
- unipolar
- bipolar affective disorder
What neurotransmitters are deficited in depression
- noradrenaline
- dopamine
- serotonin
What are the treatments for depression
- monoamine reuptake inhibitors
- Monoamine oxidase inhibitors (MAOIs)
- miscellaneous antidepressants
- electoconvulsive therapy (ETC)
- mood-stabilising drugs
Give examples of monoamines reuptake inhibitors
- TCAs: tricyclics antidepressants
- SSRIs: selective serotonin reuptake inhibitors
- SNRIs: serotonin/noradrenaline reuptake inhibitors
What are the harmful effects of CO
- highly toxic
- 50% of fatal poisoning
- long term neurological & cardiovascular disorders
What are the benefits of CO
- endogenous signalling molecule
- cardioprotective
- neuroprotective
what is the role of antidepressants
increase monoaminergic transmission within the synaptic cleft
