Intro To Cell Physiology And Pharmacology

Question 1

Extra cellular signalling molecules

Answer 1

Main Extracellular Signalling Groups
Endocrine
Paracrine
Autocrine

Characterised by distance/volume over which signalling molecules act

Overlap between categories sites of action

Suffix - crine from Greek ‘krinein’ to separate or distinguish

Question 2

Endocrine system

Answer 2

Endocrine Signalling Molecules
Secreted into blood stream : ‘Global’ signal route - circulation to whole body
Highly potent - picomolar to nanomolar range (10-12 M to 10-9 M)

Timescale of action ranges from seconds to months (molecule/receptor dependent)

In health - synthesis release and degradation well controlled - subject to tight feedback control

Close interaction synchrony and integration between endocrine signalling is key e.g. controlling ovulation or blood sugar (insulin/glucagon)

Major Types of Signalling Molecules
Hydrophilic 1 - Amines - Amino acid derivatives – small charged hydrophilic with Receptors in Plasma Membrane
Hydrophilic 2 - Peptides to Proteins - Common derivation from cholesterol Receptors are Intracellular
Lipophilic - steroids
Short chain to many e.g. Insulin 51 a.a.s  5.8 kDa with Receptors in Plasma Membrane

Question 3

Paracrine signalling molecules

Answer 3

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

Communication scale reduction by 10-2 to 10-7

Paracrine signalling molecules released into extracellular environment

Induce changes in receptor cells - specific behavior / differentiation

Examples - Very wide set of signalling molecules
In ICPP: Neurotransmitters - neurone to neurone

Neurotransmitters - Tight coupling of signalling molecule transmission over synapse – one way transmission of signal

Primary Signalling Role - Excitatory - signal increase firing rate post synaptically
Inhibitory - signal decrease firing rate post synaptically

Neurones can summate both kinds of input ‘accelerate’ and ‘brake’ fine control

Question 4

What happens when a signalling molecule binds to its target

Answer 4

Endogenous and exogenous signalling molecules bring about a change in functional status of target cells – this is what they are meant to signal

This function can be to transform an earlier signal to produce another chemical or electrochemical signal - perform and contribute to signal processing

Perform a signal dependent specific task e.g. transport or synthesis

Question 5

Overview of signalling molecules targets

Answer 5

Majority of drug targets can be classified using the mnemonic  RITE
Receptors 
Ion channels 
Transporters 
Enzymes 

Important exceptions in chemotherapy where target is a structural
protein or DNA

Distinction is aiming to selectively kill another organism - antibiotics for bacteria: or specific cell type - cancer cells in patients

Classification is not ‘strict’ - more ‘fluid’ with Ion Channels includes
Ligand Gated
Voltage Gated
Modulated by GPCR activity/allosteric modulation

Different types of receptor 
KING
Kinase linked receptors 
Ion channels 
Nuclear/intracellular 
G-proteins coupled receptors