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Physiology > cell signalling - week 2 - part 1 > Flashcards

cell signalling - week 2 - part 1 Flashcards

1
Q

Why do cells need to signal? (7)

A
  • cell fate and decision making
  • growth
  • division
  • motility
  • secretion
  • metabolism
  • death
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2
Q

How do cells communicate?

A
  • via chemical messengers
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3
Q

What are chemical messengers also known as?

A

signalling molecules

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4
Q

What exactly is the signal?

A

a ligand for a receptor

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5
Q

Where can messages be sent to?

A
  • direct neighbouring via contact
  • surrounding cells via diffusion
  • much longer ranges
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6
Q

How does a cell respond to a signal?

A
  • quickly via altered protein function
  • slowly when changing gene expression
  • both causes a cellular response
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7
Q

Why do we need membrane bound receptors?

A

2nd messenger is changed or produced in response to a primary messenger

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8
Q

Name the most common secondary messengers?

A

cAMP
cGMP
Ca2+
IP3
Nitric oxide
lipid metabolites

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9
Q

How do signals pass information?

A
  • indirectly between more distant cells or directly between ada cent cells
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10
Q

Name four different ways in which signals can pass indirectly between more distant cells

A
  • autocrine - cell to itself
  • paracrine - cell to its neighbourhood
  • endocrine - cell to another cell at a distance
  • neuronal - via nervous system
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11
Q

Describe indirect cell signalling

A
  • diffusion based
  • chemical messenger/ signalling molecule secreted form a cell
  • most molecules are secreted into aqueous fluid
  • molecules transported over rein of distance
  • signal binds to target receptor
  • binding of signal causes response in target cell
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12
Q

Give examples o aqueous fluids most molecules are secreted into

A
  • extracellular fluid,
  • lymph
  • blood
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13
Q

Give examples of where the target receptor the signal is going to bind to can be located

A
  • inside the cell
  • on the cell membrane
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14
Q

Describe autocrine signalling

A
  • cell which producing ligand is also the target cell responding to the signal
  • single leaves, but does not diffuse far (few microns only)
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15
Q

Describe paracrine signalling

A
  • signalling cell send a signal to its direct neighbours
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16
Q

In paracrine signalling do the signalling cell and the target cell have to touch?

A

no

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17
Q

How far does the signal travel during paracrine signalling?

A
  • short distances, normally in the same tissue
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18
Q

Give an example of paracrine signalling

A

immune cell recruitment and inflammation by mast cells:
- allergic reactions
- mast cells produce histamine which causes an inflammatory response

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19
Q

Describe endocrine signalling

A
  • target cell and signalling cell separated by large distance
  • gland secretes a hormone
  • transported in circulatory system or lymph/ECF
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20
Q

Which routs can a signal take in endocrine signalling?

A

circulatory system (blood) but also lymphatic or ECF

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21
Q

Describe neural signalling

A
  • nerve impulses travel long distances as electric impulses (fast) - action potentials
  • chemical messages travel very short distance (slower) - synaptic transmission
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22
Q

How fast is the autocrine system?

A

shortest distance - msec to secs

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23
Q

How fast is the paracrine system?

A

shortest distance - msec to secs

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24
Q

How fast is the endocrine system?

A

long distance - secs to mins, maybe hours or even days

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25
Q

how fast Is the neural system?

A

long distances - mecs

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26
Q

name ways in which signals can pass information in direct ways between adjacent cells

A
  • gap junction signalling
  • juxtracirne signalling
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27
Q

Explain gas junction signalling

A
  • signal pass via gap junctions form cytoplasm of one cell into cytoplasm of the next
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28
Q

how many connexions/ hemichannels does a gap junction require?

A

2

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29
Q

What is a hemichannel/ connexion made up of? How many?

A

6 connexin proteins

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30
Q

Does juxtracrine signalling require signal molecule movement?

A

No

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31
Q

How can signalling molecules be classified based on their biophysical properties?

A

either hydrophilic (soluble in aqueous solutions, eg. blood and lymph)
or hydrophobic (insoluble in hydrophilic solutions)

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32
Q

What allows hydrophilicity?

A

ability to travel directly in the blood, extracellular fluid or lymph

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33
Q

What does hydrophobicity require?

A

solubilisation by transport proteins in order to be secreted and travel to their target cell

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34
Q

What kind of receptor is targeted by hydrophobic signals?

A

generally intracellular (nuclear) receptors

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35
Q

What kind of receptor is targeted by hydrophilic signals?

A

generally, plasma membrane bound receptors, as the signal molecule is unable to pass through the lipid bilayer

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36
Q

name the 6 major classifications of signalling molecules

A
  • peptides
  • amines
  • steroids
  • lipids
  • purines
  • gases
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37
Q

Are peptides hydrophilic/hydrophobic?

A

hydrophilic

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38
Q

Are amines hydrophilic/hydrophobic?

A

either hydrophilic or hydrophobic

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39
Q

Are steroids hydrophilic/hydrophobic?

A

hydrophobic

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40
Q

Are lipids hydrophilic/hydrophobic?

A

hydrophobic

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41
Q

Are purines hydrophilic/hydrophobic?

A

hydrophilic

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42
Q

Are gases hydrophilic/hydrophobic?

A

hydrophilic

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43
Q

What three classes make up all known hormones and most of the known neurotransmitters?

A

first three - peptides, amine, steroids

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44
Q

What include peptides?

A
  • single amino acids
  • true peptides (at least 2 aa)
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45
Q

What can singe aa’s function as?

A

neurotransmitters

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46
Q

name three examples of neurotransmitters made up by a single amino acid

A

aspartic acid, cysteine, glutamic acid

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47
Q

How is glutamic acid processed?

A

via decarboxylation to form GABA

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48
Q

name examples of true peptide signals

A

neurotransmitters such as endorphin and hydrophilic hormones such as oxytocin

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49
Q

Where are all peptide signal molecules synthesised?

A
  • translated from mRNA in the rER
  • subject to post translational modification in Golgi
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50
Q

name examples of post translational modifications in the Golgi apparatus

A
  • glycosylation - carbohydrate groups are added to a protein following its translation
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51
Q

How are peptide signal molecules transferred after the Golgi

A
  • packaged into secretory vesicles
  • released into extracellular space via exocytosis
  • release either immediate or after some time
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52
Q

name a peptide signal molecule which is transferred out of the cell immediately after synthesis

A

cytokines

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53
Q

name a peptide signal molecule which is stored before release out of the cell

A

hormones and neurotransmitters

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54
Q

How do peptide signals act?

A

via cell surface receptors nd may have a number of different effects

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55
Q

Name two types of cell surface receptors

A

ionotropic and metabotropic

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56
Q

what if the membrane receptor is ionotropic?

A

binding of the signal to the receptor results in a change in ion flux into the cell

57
Q

what if the membrane receptor is metabotropic?

A

binding of ligand to receptor results in a change in an enzyme’s activity within the cell

58
Q

How do we stop the peptide signal from activating the receptor continually?

A

protease/peptidase enzymes are present to degredade the signal

59
Q

What is the difference in degradation between simple and complex peptide signals?

A
  • simple: rapid, signal may have a half life of only a few secs
  • complex: eg. glycoproteins, slower, yield a half life measured in hours
60
Q

if the half life of the protein signal is longer what does that mean regarding its synthesis?

A

they need to be continually synthesised by signalling cell in order to have a sustained signalling effect

61
Q

What are biogenic amines?

A
  • molecules, which contain an amine group (NH2)
  • usually derived from amino acid
62
Q

What amine is derived from tyrosine, is it hydrophilic/hydrophobic?

A

catecholamines (dopamine, octopamine, noradrenaline, adrenaline)
- hydrophilic -

63
Q

What amine is derived from tyrosine derivative (thyronine), is it hydrophilic/hydrophobic?

A

thyroid hormone (thyroxine)
- hydrophobic -

64
Q

What amine is derived from tryptophan, is it hydrophilic/hydrophobic?

A

indoleamines (serotonin and melatonin)
- hydrophilic -

65
Q

What amine is derived from histidine, is it hydrophilic/hydrophobic?

A

histamine
- hydrophilic -

66
Q

What amine is derived from choline, is it hydrophilic/hydrophobic?

A

acetylcholine
- hydrophilic -

67
Q

Where is the neurotransmitter dopamine found?

A

in all taxa

68
Q

Where is the neurotransmitter octopamine found?

A

invertebrates

69
Q

Where is the neurotransmitter noradrenaline found?

A

vertebrates

70
Q

What is adrenaline and where is it found?

A

both paracrine and endocrine hormone found in vertebrates

71
Q

What is an example of indoleamines?

A
  • serotonin (5HT)
  • acts via 5HT receptors on plasma membrane
72
Q

What can 5HT also be metabolised into?

A

melatonin
- neurotransmitter in most taxa
- associated with regulation of circadian and seasonal rhythms in vertebrates
- strong association with seasonal affective disorder (SAD)

73
Q

Describe histamine

A
  • neurotransmitter and also a paracrine signalling molecule in all taxa
  • ## acts via a number of different plasma membrane receptors (diff response, diff tissue)
74
Q

What effect does histamine have in vascular tissue?

A

results in vasodilation

75
Q

What effect does histamine have in the bronchus?

A

results in bronchoconstriction

76
Q

What is histamine also known for?

A

as a chemoattractant for mast cells - strongly associated with allergic responses

77
Q

Acetylcholine is found in all taxa. Describe the receptors acetylcholine acts on

A
  • acts via plasma membrane receptor
  • nicotine ACh receptors are ionotropic, respond to signal binding by allowing ion flux into receiver cell
  • metabotropic ACh receptors funciton by altering the metabotropic receptor GPCR
78
Q

Where and in what form are thyroid hormones found?

A
  • unique to vertebrates
  • hydrophobic
  • very small portion (<1%) free in blood, majority requires a carrier protein Ito be soluble within an aqueous fluid
79
Q

Give an example of a thyroid hormone carrier protein and explain how they function?

A
  • thyroxine binding globulin and albumin
  • function by activating nuclear receptors which increases basal metabolic rate
80
Q

What are steroids?

A

signal molecules that derive from cholesterol (hydrophobic 27C molecule)

81
Q

In what forms do steroids exist?

A
  • class of endocrine and paracrine hormones in all vertebrates (sex hormones) and many invertebrates (ecdysone)
  • pheromones (communication between organisms)
82
Q

name the five classes of steroid hormones

A
  • progestins
  • glucocorticoids
  • mineralocorticoids
  • androgens
  • estrogens
83
Q

give an example of a progestin, how many carbons?

A

progesterone (21C)

84
Q

Give an example of a glucocorticoid, how many carbons?

A

cortisol (21C)

85
Q

Give an example of a mineralocorticoid, how many carbons?

A

aldosterone (21C)

86
Q

Give an example of an androgen, how many carbons?

A

testosterone (19C)

87
Q

Give an example of an estrogen, how many carbons?

A

estradiol (18C)

88
Q

All steroid hormones have 21 C true or false?

A

false - testosterone (19C), estradiol (18C)

89
Q

Where are steroids synthesised?

A

mitochondria and sER

90
Q

What attributes do all these steroid molecules have?

A

lipophilic
hydrophobic

91
Q

What does it mean that all these steroid molecules are lipophilic?

A
  • soluble in plasma membrane -> cannot be stored within vesicles or within cells
    -> synthesised immediately prior to secretion
92
Q

what does it mean that all these steroid molecules are hydrophobic?

A
  • insoluble in aqueous fluids which surrounds cell
  • to travel to site of action, require binding to carrier protein
93
Q

What are common carrier proteins for steroid signalling molecules (hormones)?

A

binding globulin or albumin

94
Q

How ua raw binding of the steroid hormone regulated to the carrier proteins?

A

by the laws of mass action and mass action equilibrium

95
Q

What do the laws of mass action and mass action equilibrium state?

A

M+C <=> MC

M= messenger molecule
C= carrier
MC = messenger/carrier complex

96
Q

What can be understood from the law of mass action equilibrium?

A
  • source of signal, where conc is highest
  • most chemical messengers will bind to carrier protein
  • these contained in circulatory system - move away from source quickly to area where unbound messenger conc. is lower
    -> unbinding f messenger form MC
  • int he unbound state again, messenger can interact with target cell
97
Q

What do steroid signals bind to?

A
  • nuclear receptors
98
Q

where can nuclear receptors be found?

A
  • in cytosol (class 1)
  • within nucleus (class 2)
  • in complex with the receptor
99
Q

In complex with receptor what do steroid signals function as ?

A

transcription factors - also known as ligand dependent transcription factors

100
Q

What are transcription factors able to do?

A

bind DNA and regulate gne expression via interactions with RNA pol

101
Q

What are rarer signalling molecules?

A

lipids, purines, gases
(only rarer, not less important)

102
Q

What are lipids, name the most important ones

A
  • hydrophobic signalling molecules
  • eicosanoids: 20C lipids
103
Q

What includes eicosanoids?

A
  • prostaglandins (PGs) and thromboxanes (TXs)
  • leukotrienes (LTs), hydroxyeicostatetraenonic acid (HETEs), hydroperoxyeicostatertraenonic acid (HPETE’s), lipoxins
104
Q

How are PGs and TXs synthesised?

A

by the action of cycloocygenase (COX)/ prostaglandin synthase (PTGS) enzymes

105
Q

How are Lts, HETEs, HPETEs and lipoxins synthesised?

A

by lipoxygenase (LOX) enzymes

106
Q

What lipids are important mediators in the inflammatory cascade? What do they do?

A

prostaglandins and leukotrienes
- signal to immune cells and vasculature

107
Q

How can you characterise leukotrienes?

A

molecules made in leukocytes
characterised by three C=C double bonds

108
Q

What is the lipid substrate for the cyclooxyrgenase and lipoxygenase pathways? Why?

A

the polyunsaturated fatty acid, arachidonic acid (AA)
- 20C fatty acid has 4 double bonds, all cis

109
Q

What is arachidonic acid notation?

A

(C20:4)

110
Q

How is arachidonic acid stored? Where?

A

esterfied (via carboxylic acid group) to glycerol in membrane phospholipids

111
Q

How do you synthesis eicosanoids?

A
  • first step: hydrolyse that ester bond,
  • liberate that AA substrate from membrane phospholipids, by the action of phospholipase A2 (PLA2)
112
Q

What do eicosanoids such as prostaglandins and leukotrienes do?

A

important for inflammatory cascade and mediating inflammation and nociception (pain signalling)

113
Q

How to limit inflammation and/ or relieve pain:

A

(1) inhibit PLA2 using anti- inflammatory steroids - eg, glucocorticoid steroid hormone cortisol, or synthetic glucocorticoids (eg. hydrocortisone)
(2) inhibit downstream PTGS/COX enzymes using non-steroidal anti- inflammatory drugs (NSAIDs) eg. aspirin, ibuprofen, paracetamol

114
Q

When prostaglandins are synthesised by AA, name their common intermediate

A

PGH2

115
Q

What does PGF2alpha induce?

A

contraction of smooth muscle (eg. in vasculature and uterine myometrium)

116
Q

How does PGF2alpha and PGE2 differ?

A
  • differs only in having a ketone rather than a hydroxyl group at C9
117
Q

What does PGE2 induce?

A

relaxes smooth muscle, acts all vasodilator rather than vasoconstrictor

118
Q

Even though lipids, prostaglandins bind to and act ia cell surface receptors, what are they also?

A

G-protein coupled receptors (GCPRs)

119
Q

How does PFG2alpha induce muscle contraction?

A
  • binds to and activates PTGFR receptors
  • these act via Gq G-protein, stimulating phospholipase C (PLC) - culminating in gen of intracellular second messenger inositol-1,4,5-trisphosphate (IP3)
  • elevates intracellular calcium (Ca2+) conc
  • induces muscle contraction
120
Q

How can PGE2’s be mediated

A
  • binds to and activates PTGER receptors - 4 cloned isoforms
  • PTGER@ and PTGER4 act via Gs G-portein
  • stimulate adenylyl cyclase (AC) - culminating ingenue of intracellular second messenger cyclic adenosine-3’,5’-monophosphate ()cAMP
  • that activates protein kinase A (PKA)
  • mediates intracellular response to PGE2
121
Q

What are all prostaglandins reliant on?

A

presence of a hydroxyl group at C15

122
Q

How do PGs rapidly inactivate?

A
  • by the short chain alcohol dehydrogenase (SCAD) enzyme, 15- hydroxyprostaglandin dehydrogenase(PGDH)
  • converting pivotal OH group at C15 to double bond ketone
  • severely limits range of action - only autocrine/paracrine rather than endocrine hormones - they would rapidly inactivate if secreted into circulation by the PGDH enzyme
123
Q

As what can the two purines, adenine and guanine exist in?

A

either nucleosides (adenosine and guanosine) or as nucleotides (AMP, ATP, GTP)

124
Q

What are purines known as?

A
  • to act as neurotransmitter or neuromodulators
  • acting locally as autocrine/ paracrine hormones
125
Q

Give an example of a purine in a mammal

A

both adenosine and extracellular ATP

126
Q

What do adenosine and extracellular ATP do in a mammal?

A
  • acting as a excitatory neurotransmitter to depolarise neurons
  • lowers heart rate and hence cardiac output by signalling to cardiomyocytes
  • autocrine action in leukocytes to modulate their activation as part of the immune response
  • paracrine action on osteoblasts and osteoclasts to remodel bone (only in vertebrate)
127
Q

How are purines limited by their metabolism?

A
  • purine nucleotides are all subject to hydrolyses by ectonucleotidase enzymes - remove sequential phosphates form the nucleotide tri- di and monophosphate
    -> limits purine to exert autocrine and paracrine (rather than endocrine) actions, or acting as neurotransmitter across synaptic cleft of purinergic neurons
128
Q

How do purines activate transmembrane signalling?

A

bind to purinergic receptors

129
Q

Where do adenosine and ATP act via?

A

metabotrophic GPCRs and also ionotropic receptors/ ligand-gated ion channels P2X receptors

130
Q

Name three actions which involve ligand-gated ion channels

A

nociception
platelet aggregation
ejaculation

131
Q

name three gases included in cell to cell communication

A
  • carbon monoxide (CO)
  • hydrogen sulphide (HS)
  • nitric oxide (NO)
132
Q

Why can gases pass through the bilayer?

A

even though they are hydrophilic, they are also very mall, so they can diffuse freely

133
Q

What type fo receptor do gas molecules interact with?

A

intracellular proteins - due to size

134
Q

How is NO synthesised?

A

form amino acid substrate arginine by NO synthase enzymes

135
Q

What’s NOs half life?

A

short - only 2 to 30 secs

136
Q

What does NOs short half life have for consequences?

A
  • act locally on autocrine and paracrine manner
  • doesn’t remain active long enough to travel any distance
137
Q

Name NOs functions

A
  • paracrine signal within immune system
  • circulatory system: acts as vasodilator
138
Q

How does NO act as a vasodilator?

A
  • NO synthesised by NOS in vascular endothelial cell
  • diffuses into vascular smooth muscle cell
  • binds to soluble isoform of enzyme guanylyl cyclase
  • this intracellular enzyme, changes confirmed on binding NO, catalyses conversion of GTP to cyclic guanosine3’,5’ monophosphate (cGMP)
  • this activates protein kinase G (PKG)
  • relates smooth muscle layer around blood vessel
  • lower blood pressure

Physiology (18 decks)

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