Biological Signalling Molecules

Question 1

What is pharmacology?

Answer 1

The study of molecular signallers regulating physiological processes

Question 2

Characteristics of endocrine signalling molecules:

Answer 2

Glands produce hormones that act as signalling molecules

Act over long distances in the body

Cells need to express receptors

Secreted into bloodstream

Highly potent (pico to nano molar range)

Question 3

What are the major types of signalling molecules?

Answer 3

Hydrophilic 1 - amines

Hydrophilic 2 - peptides to proteins

(Receptors in plasma membrane for both)

Lipophilic - steroids (receptors are intracellular)

Question 4

Exogenous endocrine analogue molecules:

Answer 4

Attempt to mimic endogenous signal molecules

Question 5

Paracrine signalling molecules characteristics:

Answer 5

Signalling coupled from cell to cell or cells within the nearby volume

Paracrine signalling molecules released into the extracellular environment

Induce changes in receptor cells

Question 6

Characteristics of neurotansmission:

Answer 6

Tight coupling of signalling molecules transmission over synapse (one way transmission)

Electrochemical - chemical signal conversion

Distance ~ 20nm

Velocity ~ msecs

Question 7

Autocrine signalling molecules…

Answer 7

Cells respond to signalling molecules they produce and release themselves

Typically act over microns when released

Question 8

Four signalling molecule targets:

Answer 8

Receptors

Ion channels

Transporters

Enzymes

RITE

Question 9

Four types of receptor:

Answer 9

Kinase linked receptors

Ion channels (ligand gated)

Nuclear/intracellular

G-protein coupled receptors

KING

Question 10

Characteristics of kinase linked receptors:

Answer 10

Mediate signals of a wide variety of protein molecules e.g. Growth factor cytokines

Act via phosphorylation of specific groups - set into motion signalling cascade ‘molecular switches’ lead to gene transcription e.g. Growth/differentiation

Question 11

Characteristics of Ion channels (ligand gated):

Answer 11

When bound with the ligand, ion hate current for the duration of the binding

Allow ion currents and voltage change driving or modulating action potential generation in neurones and contraction in muscle

Coupled to Ca signalling when LGIC

Question 12

Characteristics of Nuclear/Intracellular receptors:

Answer 12

Ligands need to be lipid soluble

When bound, ligand receptor complex migrates to the nucleus then binds to the gene transcription factor

Activates/inactivated/set of genes

Other ligands - thyroid hormone, vit D, xenobiotics

Question 13

Characteristics of G-protein couples receptors:

Answer 13

Largest receptor group ~ 400

E.g. Hormones, opiates

Slow neurotransmitters - muscarinic ACh, adrenoceptors, seratonin, dopamine

Three major types Gs, Gi, Gq activate different intercellular signalling routes

Question 14

What do ion channels do?

Answer 14

Selectively allow ion current to flow across the plasma membrane

Na, K, Ca, Cl

Regulate voltage signals in excitable cells and maintain membrane potential

Each ion channel family has a range of members with variation in structure/function

Question 15

Ion channels …

Answer 15

Enable selective flow of ion current down its electro chemical gradient

Question 16

Ion channel activity can be regulated by…

Answer 16

Change in electric field density

Facilitated or inhibited by phosphorylation of intracellular sites on channels

Intracellular signalling molecules (ATP, GTP, Ca)

Binding with exogenous channel blockers

Question 17

What do transporter/carrier proteins do?

Answer 17

Transport of ions/small molecules using channels facilitated diffusion

Needed if going against gradient

Use ATP or pre-existing gradient as energy source

Examples: GI tract, renal tubule, blood brain barrier