L9 Intercellular Signalling

Question 1

Why do cells need to communicate? [4]

Answer 1

Communication with neighbouring cells

Adaption of metabolism and nutritional requirements to the nutritional state of the body

To induce/decease Growth (division) if the need arises

Respond to danger signals

Question 2

When new cells are needed, stem cells must… [2]

Answer 2

Upregulate proliferation by the right amount

Differentiation to the desired cell type

Question 3

Intercellular signalling usually involves… [5]

Answer 3

Synthesis and release of the signalling molecule

Transport of the signalling molecule to the target cell

Detection of the signal by a specific receptor

A change in cellular behaviour triggered by activation of the receptor (activated by intracellular signalling)

Removal of the signal, which often terminates the cellular response. In some cases this may be removal of the receptor.

Question 4

Types of intercellular signals [4]

Answer 4

Proteins e.g. Interferon, insulin

Peptides e.g. glucagon, growth hormone produced by cleavage of proteins

Small chemicals: steroids, made from cholesterol e.g. estradiol, cortisol
amino acid metabolites e.g. adrenaline, histamine

Dissolved gases e.g. Nitric oxide

Question 5

For cell to respond to signal, what must happen? [3]

Answer 5

Ligand must be present
Responding cell must have corresponding receptor
Receptor must be correctly coupled to intracellular signalling pathway

Question 6

Signalling molecule that binds receptor is called…

Answer 6

Ligand

Question 7

Importance of cell surface receptors [3]

Answer 7

Most signalling molecules are too large/hydrophilic to cross membrane

Ligand binding changes activities of intracellular domains of receptor - initiate response

Signalling molecule does not need to enter cell

Question 8

Categories of membrane receptors [3]

Answer 8

Receptors linked to ion channels
G protein coupled receptors
Receptors linked to enzymes

Question 9

Receptors can be located in [2]

Answer 9

cytosol or nucleus

Question 10

How do small molecules cross?

Answer 10

Small molecules (e.g. Nitric oxide) and hydrophobic molecules(e.g. steroid hormones, thyroxin) can cross the cell membrane and directly bind to receptors in the cytosol or the nucleus

Question 11

Different responses to the same signal - example?

Answer 11

Different cells responses vary

Adrenaline: Causes SM contraction in BV of gut BUT relaxation of SM in BV of muscles

Opposite actions due to different adrenergic receptors
]
Alpha contract and beta relax in muscles

Question 12

Muscarinic type

Answer 12

G protein coupled receptor

Question 13

Nicotinic

Answer 13

Na+/K+ channel

Question 14

Short range signalling

Answer 14

Endocrine, paracrine, neuronal, autocrine and juxtracrine signalling

Question 15

Long range signalling

Answer 15

Endocrine

Question 16

Endrocine signalling - how does it work?

Answer 16

• Hormone: Compound produced by endocrine gland and released into bloodstream
• Acts on target cells at a distance location
• Hormone circulating in blood coming into contact with most cells within body
• Only a limited number of cells can respond to a hormone
• Must express the correct receptor to interpret the signal
Hormones regulate cell reactions by affecting gene expression

Question 17

Endocrine signalling importance in metabolism

Answer 17

Pancreas: Beta cells = insulin, alpha cells = glucagon
Type 1 diabetes: no insulin
Type 2 diabetes: absent or decreased response to insulin by target cells

Question 18

Endocrine signalling importance in stress response

Answer 18

The glucocorticoid receptor (GR) can both activate and suppress gene expression producing both metabolic and anti inflammatory effects

Question 19

Clinical uses of steroids

Answer 19

• Synthetic hormones that activate glucocorticoid receptor: Hydrocortisone, prednisolone and dexamethasone
• Autoimmunity - psoriasis, ulcerative colitis
• Allergic reactions - urticaria
Asthma

Question 20

Paracrine signalling - how does it work?

Answer 20

• Signalling molecule released from one cell and diffuse locally to neighbouring cell
• Proteins: cytokines (generate immune response) and platelet-derived growth factor (stimulate cell proliferation)
• Amino acid derivative: Histamine promotes local inflammation
Dissolved gas: Nitric oxide relaxes smooth muscle, dilates BVs (arginine derivative)

Question 21

Nitric oxide and paracrine signalling

Answer 21

NO produced from arg when BV wall endothelial cells are stimulated by Ach

NO diffuses into nearby smooth muscle cells and activates its target enzyme guanylate cyclase

Question 22

Nitric oxide and cGMP

Answer 22

• NO binds to guanylyl cyclase, and activates it to make cyclic GMP from the nucleotide GTP
• Cyclic GMP causes the smooth muscle cells to relax, and thus increases blood flow through the blood vessel
The effect is short-lived, as the cyclic GMP is quickly hydrolysed to GMP by phosphodiesterase (half-life ~10 seconds)

Question 23

Angina treatment

Answer 23

Nitroglycerin

Question 24

Neuronal signalling - how?

Answer 24

Neurotransmitters travel only across the synaptic gap to the adjacent target cell only

Adrenaline: regulates attentiveness and mental focus as neurotransmitter vs blood redirection and glycogen->glucose conversion as a hormone

Question 25

Neurotransmitter examples [4]

Answer 25

Acetylcholine - released by motor neurons innervating muscle cells

Serotonin - trp derivative and modulates mood

Dopamine - tyr derivative and fine-tuning of motion

Endorphins - peptide (released during pain inducing analgesia)

Question 26

Autocrine signalling - how?

Answer 26

Cells secrete signalling molecules that bind their own receptors

Many cytokines produced by immune cells can activate the release cell, amplifying activation of that cell which increases cytokine production

Question 27

Juxtacrine signalling - how?

Answer 27

• Contact-dependent signalling - immediate neighbours signal each other via membrane bound molecules
• Gap junctions - channels form between cells - diffusion of ions, nucelotides and sugars
Contact-dependent receptor ligand binding - direct cell to cell communication/interaction with extracellular matrix

Question 28

Gap junctions - what are they?

Answer 28

• Gap junctions provide neighbouring cells with a direct communication link that can be opened or closed in response to the cell environment similar to an ion channel
• Gap junctions are formed by channels called connexons
• connexons consist of 6 protein subunits
• 20 types of subunit exist
Connexons can be built from the same or different subunits

Question 29

Importance of gap junctions

Answer 29

Gap junctions between heart muscle cells allow waves of electrical excitation to pass quickly through the tissue
Gap junctions appear in the myometrium of the uterus towards to the end of pregnancy ,where they help coordinate uterine contractions during childbirth