Pharmacology- Biological Basis for Therapy (incomplete)

Question 1

What is a receptor?

Answer 1

sensing elements of chemical communication in the body

Question 2

Receptors targets

Answer 2

neurotransmitters, hormones, other mediators and many therapeutic agents

Question 3

chemical signalling of autocrine cells

Answer 3

cell signals to itself

Question 4

chemical signalling of paracrine cells

Answer 4

cell signals to its close neighbours

Question 5

chemical signalling of endocrine cells

Answer 5

Cell signals via molecules transported by the blood to target distant cells

Question 6

Major types of receptors

Answer 6

• Ligand gated ion channels/ inotropic receptors
• G protein coupled receptors/ metabotropic receptors
• kinase-linked receptors/ enzyme-linked receptors
• nuclear receptors

Question 7

Ligand gated ion channels/ inotropic receptors

Answer 7

found at plasma membrane

targeted by hydrophilic signalling molecules eg acetylcholine

act on a ms timescale

Question 8

G coupled protein receptors/ metabotropic receptors

Answer 8

found at plasma membrane

targeted by hydrophilic signalling molecules eg

signal on a s timescale

Question 9

kinase linked receptors/ enzyme linked receptors

Answer 9

found at plasma membrane

targeted by hydrophilic protein mediators eg insulin

work on an hr timescale

Question 10

nuclear receptors

Answer 10

found intracellularly in the nucleus (or cytoplasm and translocate to nuclease when activated by agonist)

targeted by hydrophobic signalling molecules

very slow action on hrs/ day timescale

Question 11

Ion channels

Answer 11

transmembrane pores formed by glycoproteins

span membrane to create ion conducting pathway for selected ions

Question 12

Gating

Answer 12

regulatory signals that cause the channel to cycle reversibly between a closed (non-conducting) state and open (conducting)

Question 13

what happens when ion channel gate is open?

Answer 13

conduct selected ions passively down their electrochemical gradients at incredible rates frequently mediating very rapid electrical signals (e.g. action potentials, synaptic potentials)

Question 14

What are ion channels gated by?

Answer 14

chemical signals (LGICs)

transmembrane voltage (VGICs)

Physical stimuli (thermal/ mechanical energy)

Question 15

Example of LGIC

Answer 15

nicotinic acetylcholine receptor of skeletal muscle and neurones

Question 16

second messenger systems

Answer 16

most cell surface receptors signal this way

it is when receptor activation modulates the activity of an effector that is generally an enzyme, by can be an ion channel

Question 17

GCPR structure

Answer 17

• integral membrane protein
• single polypeptide with ec NH2 and ic COOH
• contains 7 transmembrane alpha helical spans
• sometimes function as dimers

Question 18

G protein

Answer 18

• peripheral membrane protein
• 3 polypeptide subunits
• contains a guanine nucleotide binding site in the alpha subunit that can hold guanosine triphosphate (GTP) or guanosine diphosphate (GDP)
• named according to their alpha subunit

Question 19

inactive G protein

Answer 19

guanine nucleotide binding site of the alpha subunit is occupied by GDP

Question 20

active G protein

Answer 20

guanine nucleotide binding site of the α-subunit is occupied by GTP and the α- and βγ-subunits separate (dissociate) from each other

Question 21

How is G protein activated?

Answer 21

agonist binds to GPCR, causes conformational change, which is transmitted to the GP alpha sub unit

this releases GDP, allowing GTP to bind in its place (guanine nucleotide exchange)

separates from the receptors and beta gamma dimer (subunits dissociation)

generates a free GTP bound alpha subunit and beta gamma dimer