PHARMACOLOGY 1

Question 1

what is a type 1 receptor?

Answer 1

fast neurotransmission - directly coupled to an ion channel – ionotropic receptors

Question 2

what is a type 2 receptor?

Answer 2

signal via G-protein pathways – metabotropic receptors

Question 3

what is a type 3 receptor?

Answer 3

signal via enzyme-linked cell surface receptors

Question 4

what is a type 4 receptor?

Answer 4

located in specialized regions of DNA, activation directly promotes gene up-regulation

Question 5

what does the nicotinic Ach receptor consist of?

Answer 5

5 memb spanning subunits - 2 alpha, beta, gamma, delta

Question 6

how does the nicotinic Ach receptor open?

Answer 6

2 Ach molecules bind to the 2 units - this opens the ligand-gated Na ion channel and depolarises the cell.

Question 7

what is intracellular signalling?

Answer 7

describes the way the binding of a ligand with a receptor activates an enzyme cascade, ultimately inducing a cellular response.

Question 8

what is the function of receptors?

Answer 8

provide a means of selectively transmitting extracellular signals across the cell membrane, enabling cells to respond to the stimuli.

Question 9

what do cellular responses include?

Answer 9

opening of ion channels, increased secretion of other signalling molecules, cell motility and modifications of the cell cycle

Question 10

what are the 2 types of intracellular signalling?

Answer 10

G-protein pathway - Type 2 receptors

enzyme-linked cell surface receptor pathway - Type 3 receptors

Question 11

what do type 2 receptors consist of?

Answer 11

most consist of a single polypeptide chain forming seven transmembrane helices arranged with an extracellular N-terminus and a cytoplasmic carboxy terminus

Question 12

where does the ligand bind in type 2 receptors?

Answer 12

binds to a binding site in the helices embedded in the memb

Question 13

what part of the receptor couples to a G-protein?

Answer 13

the 3rd loop

Question 14

what are G-proteins?

Answer 14

Exist as highly mobile proteins in the membrane

Question 15

what do G-proteins consist of?

Answer 15

consist of 3 subunits, alpha, beta and gamma

Question 16

what does the alpha subunit function as?

Answer 16

as a GTPase, converting GTP to GDP

Question 17

what do the beta and gamma subunits do?

Answer 17

and  subunits form a complex, are very hydrophobic and stay closely associated with the memb

Question 18

what happens when the protein is inactivated?

Answer 18

the alpha, beta and gamma subunits form a complex in which GDP is bound to an alpha subunit

Question 19

what is the 1st stage of G protein activation?

Answer 19

Binding of a ligand to the receptor - allows a conformational change in the alpha, beta and gamma complex, allowing the alpha to exchange the GDP for a GTP and this causes the alpha to dissociate from the beta and gamma and subunits.

Question 20

what is the 2nd stage of G protein activation?

Answer 20

The  coupled to the GTP then associates with specific allosteric target enzyme such as an adenylate cyclase.

Question 21

what is the 3rd stage of G protein activation?

Answer 21

The  hydrolyses GTP into GDP. This inactivates the enzymatic ability of the  alpha subunit whilst allowing the activation of the target enzyme. The inactive alpha subunit then re-associates with the beta and gamma complex

Question 22

what can the G protein mechanism act as?

Answer 22

as a signal amplifier - a single activated receptor can activate several G proteins.

Question 23

what are the targets for G proteins?

Answer 23

Adenylate cyclase
Guanylate cyclase
Phospholipase C/inositol phosphate system
The regulators of ion channels

Question 24

what does adenyl cyclase produce?

Answer 24

intracellular cAMP

Question 25

what does guanyl cyclase produce?

Answer 25

intracellular cGMP

Question 26

what does activated adenyl cyclase do?

Answer 26

converts ATP into cAMP

Question 27

what is cAMP?

Answer 27

cyclic 3’,5’-adenosine monophosphate, cAMP functions as a secondary messenger and is inactivated by hydrolysis into 5’-AMP.

Question 28

how does cAMP act?

Answer 28

targets inactive protein kinases, activating them

Question 29

what do the activated protein kinases do?

Answer 29

use ATP as a source of phosphate groups and phosphorylate downstream enzymes thus activating them.

Question 30

give an example of cAMP's role

Answer 30

cAMP role in beta adrenoceptor activated breakdown of glycogen

Question 31

how is cAMP inactivated?

Answer 31

by phosphodiesterase. Inactivation can be inhibited by drugs such as caffeine.

Question 32

what is the phosphoinositide system?

Answer 32

based on memb phospholipid phosphoinositide (4,5) diphosphate (PIP2)

Question 33

what is the role of PIP2?

Answer 33

acts as a substrate for a membrane-bound enzyme phospholipase C (PLC) which spits PIP2 into diacylglycerol (DAG) and inositol (1,4,5) triphosphate InsP3.

Question 34

what are the secondary messengers in the phosphoinositide system?

Answer 34

DAG and InsP3

Question 35

what do DAG and InsP3 do?

Answer 35

DAG results in protein kinase C activation and InsP3 promotes Ca2+ release from intracellular stores

Question 36

how does InsP3 work?

Answer 36

binds to endoplasmic receptors and opens endoplasmic Ca2+ channels. This allows the release of Ca2+ into the cytosol where the Ca2+ can interact with a whole range of targets

Question 37

what is Ca important in?

Answer 37

Muscle contraction Control of secretion from exocrine glands (ie., the muscarinic ACh receptor) Hormone release

Question 38

what does DAG activate?

Answer 38

activates PKC which is a serine/threonine kinase and acts by phosphorylating downstream target enzymes.

Question 39

what things are associated with the PKC being activated?

Answer 39

Muscle contraction Inflammatory response Increased neurotransmitter release

Question 40

what effect do G-proteins have on ion channels?

Answer 40

directly activate ion channels, ie., interaction of ACh and muscarinic receptors opens potassium channels via a G-protein pathway

Question 41

how does the guanyl cyclase receptor work?

Answer 41

Extracellular domain binds the ligand. | On binding ligand, intracellular domain (the guanylyl cyclase) becomes activated and produces cyclic GMP.

Question 42

what does cyclic GMP do?

Answer 42

binds to cyclic GMP-dependent protein kinase (G-kinase)

Question 43

what does G-kinase do?

Answer 43

phosphorylates downstream proteins on either threonine or serine residues

Question 44

what is the secondary messenger in the guanyl cyclase receptor system?

Answer 44

cyclic GMP

Question 45

give an example of guanylyl cyclase receptor

Answer 45

the receptor for atrial natriuretic peptide.

Question 46

what are type 3 receptors?

Answer 46

Trans-Memb proteins possessing an extracellular ligand binding domain and a cytoplasmic domains that have an intrinsic enzymatic activity.

Question 47

what are the 4 kinds of type 3 receptors?

Answer 47

tyrosine kinases Receptor linked tyrosine kinases tyrosine phosphatases serine/threonine kinases