FORM & FUNCTION (Signalling) Flashcards
types of signal transmission
- Direct: cells are connected
>gap junctions
>contact-dependent - Indirect: cells are not connected
>Paracrine
>hormonal
gap junctions (direct)
-epithelial cells
-heart muscle and smooth muscles
-essentially all tissues where cells touch each other
contact-dependent (direct)
-juxtacrine signalling
-cells NEED to make direct physical contact through a signal molecule on the PM
-important during embryonic development
>allows adjacent cells to differentiated into a different cell-type
paracrine signalling
-signals are transmitted in the interstitial fluid (diffus locally through extracellular fluid)
-only nearby cells are affected
Ex. inflammation, wound healting
paracrine signalling types
-autocrine
-between neurons
autocrine
-type of paracrine signalling
-cells respond to local signal produced by themselves
-important in development where cell gets its own signal to develop into correct tissues
Ex. interleukins released by T-helper cells can signal themselves to self-amplify
neural signalling
-type of paracrine signalling
-can travel far
-very fast (in ms)
-affect post synaptic neurons
-signals can be released into the blood stream (neuroendocrine)
hormonal signalling
-hormones released by endocrine cell
-signal molecules travel in blood stream to target cells
-not ver fast, but more FLEXIBLE since signals can affect they cells that express the receptors
hormonal signalling receptors
-must have a very high affinity for the hormon as hormones get diluted in blood
type of signal molecules
- Lipid-insoluble
- Lipid-soluble
- Gaseous-cardiovascular
- Intracellular messengers
lipid-insoluble
-amino acids (glutamate, aspartate)
-modified amines (biorgenic amines)
-peptides/proteins (less than 50AA)
-non-coding RNA
modified amines (lipid-insoluble)
- Tyrosine: catecholamines
-dopamine
-NE (primary NT of post synaptic neurons in SNS)
-E (sympathetic hormone) - Histamine (from histidine)
- Serotonin (from tryptophan)
lipid soluble
- Biogenic amine (modified AA): thyroid
- Steroids (estradiol, testosterone, cortisol)
- eicosanoids
eicosanoids
-made from arachidonic acid (component of PM) from 2 pathways
1. Cyclooxygenase (COX) pathway
2. Lipoxygenase pathway
cyclooxygenase (COX) pathway
-prostaglandins
-prostacyclins
-thromboxanes
lipoxygenase pathway
-leukotrienes
Gaseous
Nitric oxide
-released by endothelial cells causes smooth muscles to relax=leads to vessel dilation=increase blood flow
-does not need a membrane transporter on the target cell
intracellular messengers
-cAMP
-IP3
-Diacylglycerol (DAG)
-Ca2+
target cell responses
-depend on chemical properties of signal molecules
-bind to either extracellular or intracellular receptor
extracellular receptor
-lipid-insoluble signal molecules
intracellular resceptor
-lipid-soluble molecules
-cytosolic or nuclear
intracellular receptor cortisol
-steroid hormone
-regulates stress response, metabolism and immune regulation
Cortisol intracellular receptor steps
- Diffuses through PM and binds to receptor in cytosol
- Cortisol/receptor complex moves into nucleus and activates target genes important in metabolism, immune responses, and stress adaptation
3 classes of cell-surface receptors
- ion-channel coupled receptors
-ligand gated channels - Enzyme coupled receptors
- G-protein coupled receptors (GPCR)
Ion-channel coupled receptor (NMJ):
-nicotinic receptor at neuromuscular junction
1. Ach release from the motor neuron
2. Ach binds to nicotinic receptor on muscle fiber
3. Ion channel opens and allows sodium ions to move (will move out of the cell)
Enzyme-coupled receptor (insulin receptor)
-tyrosine kinase (adds P group)
1. Insulin binds and activates receptor (triggers dimerization and autophosphorylation)
2. The activation recruits and activates other intracellular proteins for cellular response
3. Translocation of glucose transporters to cell membrane (allows cells to uptake glucose from blood stream)
GPCR
-trimeric G-protein is the first molecular switch
-activated G-protein: when GDP on alpha subunit is turned to GTP
GPCR ‘steps’
- Directly open a channel
- Activate an enzyme that generates second messengers to amplify primary response
>adenylyl cyclase generates cAMP
>phospholipase C generates IP3, diacylglycerol (DAG) and Ca2+
Phosphodiesterase
-a common drug target
-degrades cAMP
Fight or flight response: SNS
- Trigger
- Primary signals
- Key targets
- Immediate effects
- Metabolic changes
SNS trigger
-perception of threats or stressor
SNS primary signals
-release E(adrenaline) and NE
SNS key targets
-heart
-lungs
-muscles
-other crucial systems
SNS immediate effects
-increase heart rate
-elevate BP
-redistribute blood flow to essential organs and muscles
SNS metabolic changes
-breakdown of glycogen to glucose for rapid energy supply
E binding to adrenergic receptor on skeletal muscle cell
1.E binds to adrenergic receptor (GPCR)
2.Triggers activation of G protein
3.G protein activates adenylyl cyclase that converts ATP to cAMP
4.cAMP (second messenger) activates a series of proteins leading to glycogen breakdown
5.Physiologically this provides more glucose more muscle cell to generate ATP for muscle contraction
GPCR that activates phospholipase C to generate IP3, DAG and Ca2
1.NE binds to alpha-1-adrenergic receptor on smooth muscle around blood vessels
2.Alpha-1 adrenergic receptors are GPCRs that activate PLC
3.Activated PLC cleaves inositol phospholipids to IP3 and DAG
4.IP3 binds to ER receptors, triggering calcium release from ER
5.DAG, along with increased calcium, activated protein kinase C (PKC)
6.PKC phosphorylates other proteins, *promotes smooth muscle contraction=vasoconstriction=increased BP
rest and digest: PNS
- Primary signals
- Key targets
- Immediate effects
- Metabolic changes
PNS primary signals
-Acetylcholine (acetyl-CoA and choline)
PNS key targets
-heart
-lungs
-muscles
-other crucial systems
PNS immediate effects
-restore heart rate
-restore BP
-redistribute blood to all organs
PNS metabolic changes
-promote glycogen storage and nutrient absorption
Ach activates GPCR on heart cells
- Ach activates GPCR on heart cells
- Activated Gbeta-gamma complex opens K+ channel
- K+ movement leads to a decrease in HR (move inside to outside cell)
Cellular response variability
-can be fast or slow
-same signalling molecule can bind to different receptors and cause different responses
signalling molecule can bind to different receptors and cause different responses (Ach examples)
- Heart pacemaker: decrease rate of firing
- Salivary glands: secretion
- Skeletal muscle: contraction
