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

Lecture One - introduction to cell signalling Flashcards

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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
what is the response time of kinase-linked receptors?
hours
26
what is the response time of nuclear receptors?
hours
27
what is an example of a ligand-gated ion channel?
nicotinic acetylcholine receptor
28
what is an example of a GPCR?
muscarinic acetylcholine receptor
29
what is an example of a kinase - linked receptor?
cytokine receptors
30
what is an example of a nuclear receptor?
oestrogen receptor
31
what is the process of ligand-gated ion channels?
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
why do ions require an ion channel?
ions require an ion channel as they are hydrophilic and cannot pass through the plasma membrane
33
what is an agonist?
a signalling molecule a hormone or a neurotransmitter
34
what is the nicotinic acetylcholine receptor?
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
what is the process of GPCR
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
what is the composition of a GPCR?
GPCR > 7 transmembrane domain receptors
37
what response occurs due to adrenaline binding to β2 adrenoceptors
bronchodilation
38
what is the process of adrenaline binding to β2 adrenoceptors?
G⍺s > stimulates adenylyl cyclase > cAMP > PKA > inhibition of MLCK activity
39
what is MLCK?
myosin light chain kinase
40
what response occurs due to adrenaline binding to ⍺2 adrenoceptors
relaxation of the GI tract (gastrointestinal tract)
41
what is the process of adrenaline binding to ⍺2 adrenoceptors?
G⍺i > inhibits adenylyl cyclase > Gβ𝛾 reacts with K+ channel > K+ leaves the cell > adrenaline dissociates
42
what response occurs due to adrenaline binding to ⍺1 adrenoceptors
vasoconstriction
43
what is the process of adrenaline binding to ⍺1 adrenoceptors?
G⍺q > stimulates phospholipase C > formation of DAGIP3 from PIP2 > increased Ca2+ concentration > stimulation of MLCK activity
44
what is signal amplification?
a quality of GPCR activation of adenylyl cyclase = continuous conversion of ATP to cAMP
45
what are adrenoceptors?
bound and activated by the hormones/neurotransmitters adrenaline and noradrenaline
46
what is the transduction method of ⍺1?
G⍺q activation of phospholipase C ↑IP3 ↑DAG
47
what is the effect of ⍺1 stimulation?
vasoconstriction of blood vessels
48
what is the transduction method of ⍺2?
G⍺i inhibition of adenylyl cyclase ↓cAMP ↑K+ channels ↓Ca2+ channels
49
what is the effect of ⍺2 stimulation?
presynaptic inhibition of noradrenaline in the central nervous system relaxation of the GI tract
50
what is the transduction method of β1?
G⍺s stimulation of adenylyl cyclase ↑cAMP
51
what is the effect of β1 stimulation?
increased heart rate and cardiac muscle contraction
52
what is the transduction method of β2?
G⍺s stimulation of adenylyl cyclase ↑cAMP
53
what is the effect of β2 stimulation?
bronchodilation increased heart rate and cardiac muscle contraction
54
what is the transduction method of β3?
G⍺s stimulation of adenylyl cyclase ↑cAMP
55
what is the effect of β3 stimulation?
thermogenesis in skeletal muscle lipolysis
56
what adrenoceptors does adrenaline bind?
binds all adrenoceptors results in a full sympathetic physiological response
57
what adrenoceptors does isoprenaline bind?
binds β1 and β2 adrenoceptors results in tachycardia and bronchodilation
58
what adrenoceptors does salbutamol bind?
binds β2 adrenoceptors results in bronchodilation used to treat the acute symptoms of asthma
59
what is the mechanism of a kinase linked receptor?
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
what is the function of kinase-linked receptors?
metabolism and growth
61
explain the insulin receptor.
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
what is the insulin signal transduction pathway?
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
what are nuclear receptors?
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
what are steroid hormones?
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
give a summary of the action of a steroid hormone.
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
give an example of a nuclear receptor and its ligand.
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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