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Cellular Communication > Lecture One - introduction to cell signalling > Flashcards

Lecture One - introduction to cell signalling Flashcards

1
Q

What is Autocrine regulation?

A

A cell communication mechanism in which the signalling molecules bind to receptors located on the cell, secreting the signalling molecules which bind to target receptors are on the same cell.
allows cell regulation and positive or negative feedback.

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2
Q

What is the process of somatostatin secretion in the stomach?

A

Somatostatin is secreted by D cells in the gastric glands
somatostatin binds to receptors - SST2R receptors on the parietal cells to inhibit adenylyl cyclase
the decrease in cAMP results in decreased gastric acid secretion from parietal cells
somatostatin also binds to SST2R receptors on the D cells themselves, resulting in a negative feedback loop and reduced somatostatin secretion.

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3
Q

What is the SST2R receptor?

A

the somatostatin type 2 receptor

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4
Q

What is cAMP?

A

cyclic AMP
the second messenger

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5
Q

What is paracrine regulation?

A

a cell communication mechanism in which the signalling molecules are secreted into the extracellular space and bind to receptors located on the adjacent cells without passing through the circulatory system.
cells are regulating the activity of adjacent cells (cells in close proximity)

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6
Q

what is the action of histamine in the stomach?

A

histamine is secreted by the enterochromaffin -like cells in the gastric glands in response to stimulation by acetylcholine
histamine binds to H2 receptors with subsequent activation of adenylyl cyclase
the increase in cAMP increases the number of proton pumps, increasing gastric acid secretion from parietal cells.
> increase in gastric acid secretion = decrease in pH.

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7
Q

What is acetylcholine?

A

part of the parasympathetic nervous system
kickstarts digestion following sympathetic response

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8
Q

what is the synapse?

A

the space between a pre-synaptic neuron and a post-synaptic neuron.

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9
Q

What is the process of synaptic transmission?

A

action potential (electrical signal) travels down the axon of the pre-synaptic neuron causing a change in voltage - depolarisation. The action potential reaches voltage-gated Ca2+ channels which are activated by depolarisation, activation changes their conformation and the ion channel pores are opened to allow calcium to flow from a high concentration out of the cell into the cell. Calcium in the cell causes synaptic vesicles which contain a neurotransmitter (signalling molecule) to move towards the synaptic cleft. Calcium binds to microtubules to push the synaptic vesicles to the synaptic cleft. The membrane of the synaptic vesicle merges with the membrane on the pre-synaptic neuron to release neurotransmitter (acetylcholine (ACh)) into the synaptic cleft. ACh binds to post synaptic receptors (nicotinic acetylcholine receptors which are permeable to sodium). Post-synaptic receptors are ligand-gated ion channels, binding of ACh causes the core of the ion channel to open allowing sodium (high conc in cleft) to travel down its electrical/concentration gradient into the post-synaptic membrane changing the intracellular sodium concentration and voltage
which triggers an action potential.

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10
Q

How is an action potential achieved?

A

an action potential is achieved by an increase in voltage.
the electrical signal is initially changed into a chemical signal, which enters the synaptic cleft and then becomes electrical again.

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11
Q

What is a neurotransmitter?

A

a neurotransmitter is a chemical substance released from a neuron
brings about the transfer of an impulse from one neuron to another neuron

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12
Q

Give examples of common neurotransmitters?

A

acetylcholine
adrenaline
noradrenaline - NA
dopamine - DA
serotonin - 5-HT
glutamate - Glu
glycine - Gly
𝛾-aminobutyric acid - GABA

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13
Q

which common neurotransmitters are also hormones?

A

Adrenaline
serotonin
histamine

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14
Q

Why can some neurotransmitters also be hormones?

A

dependent upon the mode of release
hormones are secreted to the circulatory system by glands
neurotransmitters are secreted due to action potentials

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15
Q

what is endocrine regulation?

A

a cell communication mechanism in which the signalling molecules are secreted from cells located in secretory glands into the circulatory system
allows for the signalling molecules to travel over a relatively large distance, eventually binding to receptors located on or in cells of a target organ or tissue

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16
Q

what is the hypophyseal portal system?

A

hormones such as ACTH are secreted from the cells of the pituitary glands into the connected circulatory vasculature

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17
Q

what is ACTH?

A

adrenocorticotropic hormone

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18
Q

what is the hypothalamic-pituitary-adrenal (HPA) axis?

A

stress (stimulation of the sympathetic nervous system)
> cerebral cortex (central nervous system)
> hypothalamus (CRH)
> anterior pituitary (ACTH)
> adrenal cortex (cortisol - steroid hormone)
> target tissue

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19
Q

what occurs due to elevated cortisol levels?

A

negative feedback on both CRH and ACTH secretion

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20
Q

what is CRH?

A

corticotropin - releasing hormone

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21
Q

what are the actions of cortisol?

A
  1. stimulates gluconeogenesis (formation of glucose from non-carbohydrate sources) in the liver in response to low plasma glucose/ starvation
  2. protein breakdown & liberation of free fatty acids
  3. immune system suppression
  4. facilitated stress response
  5. maintains blood pressure
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22
Q

what are the four receptor types (superfamilies)?

A
  1. ligand-gated ion channels (ionotropic receptors)
  2. G-protein coupled receptors (metabotropic)
  3. kinase - linked receptors
  4. nuclear receptors
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23
Q

what is the response time of ligand-gated ion channels?

A

milliseconds

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24
Q

what is the response time of G-protein couled receptors?

A

seconds

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25
Q

what is the response time of kinase-linked receptors?

A

hours

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26
Q

what is the response time of nuclear receptors?

A

hours

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27
Q

what is an example of a ligand-gated ion channel?

A

nicotinic acetylcholine receptor

28
Q

what is an example of a GPCR?

A

muscarinic acetylcholine receptor

29
Q

what is an example of a kinase - linked receptor?

A

cytokine receptors

30
Q

what is an example of a nuclear receptor?

A

oestrogen receptor

31
Q

what is the process of ligand-gated ion channels?

A

a signalling molecule (hormone or neurotransmitter) binds to the receptor opening the pore of the ion channel causing depolarisation due to an increase in intracellular ion concentration
the receptor is an ion channel surrounded by protein subunits

32
Q

why do ions require an ion channel?

A

ions require an ion channel as they are hydrophilic and cannot pass through the plasma membrane

33
Q

what is an agonist?

A

a signalling molecule
a hormone or a neurotransmitter

34
Q

what is the nicotinic acetylcholine receptor?

A

example of ligand-gated ion channel
composed of five protein subunits
nonspecific cation channels > permeable to Na+, K+, and Ca2+
modulate fast synaptic excitation

35
Q

what is the process of GPCR

A

ligand binds to GPCR causing a conformational change
G-protein is activated by GTP replacing GDP
the ⍺-subunit dissociates and activates adenylyl cyclase which catalyses the formation of cyclic AMP (cAMP) from ATP
cAMP activates protein kinase A which exists in an R2C2 complex. binding of 4 caMP molecules to the two regulatory subunits, releases the catalytic subunits which phosphorylate proteins in the cytoplasm
GTP dissociates to GDP which inhibits adenylyl cyclase.

36
Q

what is the composition of a GPCR?

A

GPCR > 7 transmembrane domain receptors

37
Q

what response occurs due to adrenaline binding to β2 adrenoceptors

A

bronchodilation

38
Q

what is the process of adrenaline binding to β2 adrenoceptors?

A

G⍺s > stimulates adenylyl cyclase
> cAMP
> PKA
> inhibition of MLCK activity

39
Q

what is MLCK?

A

myosin light chain kinase

40
Q

what response occurs due to adrenaline binding to ⍺2 adrenoceptors

A

relaxation of the GI tract (gastrointestinal tract)

41
Q

what is the process of adrenaline binding to ⍺2 adrenoceptors?

A

G⍺i > inhibits adenylyl cyclase
> Gβ𝛾 reacts with K+ channel
> K+ leaves the cell
> adrenaline dissociates

42
Q

what response occurs due to adrenaline binding to ⍺1 adrenoceptors

A

vasoconstriction

43
Q

what is the process of adrenaline binding to ⍺1 adrenoceptors?

A

G⍺q > stimulates phospholipase C
> formation of DAGIP3 from PIP2
> increased Ca2+ concentration
> stimulation of MLCK activity

44
Q

what is signal amplification?

A

a quality of GPCR
activation of adenylyl cyclase = continuous conversion of ATP to cAMP

45
Q

what are adrenoceptors?

A

bound and activated by the hormones/neurotransmitters adrenaline and noradrenaline

46
Q

what is the transduction method of ⍺1?

A

G⍺q
activation of phospholipase C
↑IP3
↑DAG

47
Q

what is the effect of ⍺1 stimulation?

A

vasoconstriction of blood vessels

48
Q

what is the transduction method of ⍺2?

A

G⍺i
inhibition of adenylyl cyclase
↓cAMP
↑K+ channels
↓Ca2+ channels

49
Q

what is the effect of ⍺2 stimulation?

A

presynaptic inhibition of noradrenaline in the central nervous system
relaxation of the GI tract

50
Q

what is the transduction method of β1?

A

G⍺s
stimulation of adenylyl cyclase
↑cAMP

51
Q

what is the effect of β1 stimulation?

A

increased heart rate and cardiac muscle contraction

52
Q

what is the transduction method of β2?

A

G⍺s
stimulation of adenylyl cyclase
↑cAMP

53
Q

what is the effect of β2 stimulation?

A

bronchodilation
increased heart rate and cardiac muscle contraction

54
Q

what is the transduction method of β3?

A

G⍺s
stimulation of adenylyl cyclase
↑cAMP

55
Q

what is the effect of β3 stimulation?

A

thermogenesis in skeletal muscle
lipolysis

56
Q

what adrenoceptors does adrenaline bind?

A

binds all adrenoceptors
results in a full sympathetic physiological response

57
Q

what adrenoceptors does isoprenaline bind?

A

binds β1 and β2 adrenoceptors
results in tachycardia and bronchodilation

58
Q

what adrenoceptors does salbutamol bind?

A

binds β2 adrenoceptors
results in bronchodilation
used to treat the acute symptoms of asthma

59
Q

what is the mechanism of a kinase linked receptor?

A

receptor becomes active and sets off parallel pathways.
insulin binds to intracellular tyrosine receptors which phosphorylates tyrosine residues
relay proteins attach to phosphorylated tyrosine residues activating multiple parallel pathways, resulting in different cellular responses.

60
Q

what is the function of kinase-linked receptors?

A

metabolism and growth

61
Q

explain the insulin receptor.

A

responds to dynamic changes in metabolism - blood glucose levels
↑blood glucose = release of insulin to liver and skeletal muscle = binds to insulin receptor = ↑glucose transporters = remove glucose from blood to liver, skeletal muscle and brain.

62
Q

what is the insulin signal transduction pathway?

A
  1. insulin binds to the tyrosine kinase insulin receptor which triggers phosphorylation of the tyrosine receptors
  2. phosphorylation activates tyrosine kinase which triggers a signal transduction pathway activating other protein kinases - specifically protein kinase B (PKB)
    2.1 PKB triggers the translocation of glucose transporter (GLUt-4) containing vesicles to the cell membrane to facilitate the diffusion of glucose into the cell
    2.2 PKB phosphorylates glycogen synthase kinase which inhibits the enzyme so glycogen is synthesised.
    PKB starts the process of glycogenesis
63
Q

what are nuclear receptors?

A

intracellular receptors that are generally bound by steroid hormones
are protein monomers located in the nucleus of the target cell, contain DNA-binding domains that allow for the control of gene transcription

64
Q

what are steroid hormones?

A

are hydrophobic/lipophilic and can pass through the plasma membrane to initiate a 2-step process :
1) activated hormone-receptor complex forms within a cell
2) the complex binds to DNA and activates specific genes - gene activation leads to production of key proteins

65
Q

give a summary of the action of a steroid hormone.

A

steroid hormone binds to hormone receptor forming the hormone-receptor complex which enters the nucleus
complex binds to receptor sites on chromatin, activating mRNA transcription
mRNA leaves nucleus
ribosomes translate mRNA into new protien.

66
Q

give an example of a nuclear receptor and its ligand.

A
  1. androgen (AR) > testosterone
  2. oestrogen (ERa,β) > 17β-oestradiol
  3. glucocorticoid (GRa) > cortisol, corticosterone
  4. progesterone (PR) > progesterone
  5. mineralocorticoid (MR) > aldosterone

Cellular Communication (3 decks)

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