Signalling Mechanisms and non receptor mediated mechanisms

Question 1

List 5 signal transduction systems

Answer 1

1- Ion channel receptors
2- Receptors linked to enzymes
3- G protein coupled receptors
4- Receptors regulating transcription
5- NO receptors

Question 2

List mechanism of ion channel receptors

Answer 2

Receptors are ion-selective channels in the plasma membrane.
Binding of agonist to the receptor →opening of the channel → alteration in membrane potential or change in intracellular ion concentration, both resulting in change in cell activity.

Question 3

2 examples of ion channel receptors + ion channels controlled

Answer 3

Nicotinic ACH receptors (Na/K channels)
GABA receptors (Cl receptors)

Question 4

Explain mechanism of action of RTKs

Answer 4

• The receptor is formed of two domains:
a. An extracellular domain, to which the agonist (e.g. insulin) binds.
b. An intracellular domain, which is a tyrosine kinase enzyme (effector).
• Binding of insulin causes 2 single tyrosine-kinases receptors to aggregate into a
dimer
with subsequent autophosphorylation. Then, the activated-
phosphorylated dimer binds to relay proteins, activating them. These relay proteins trigger the cellular response through either production of a second messenger or turning on gene expression.

Question 5

Structure of G proteins

Answer 5

Alpha, Beta and Gamma subunits forming a trimeric structure

Question 6

Which receptors are linked to Gs proteins?

Answer 6

Beta receptors

Question 7

Effectors regulated Gs proteins

Answer 7

Activates adenylyl cyclase, leading to cAMP formation, activating PKA and leading to a phosphorylation cascade

Question 8

List receptors linked to Gi proteins

Answer 8

Alpha 2 receptors
M2 receptors

Question 9

Effector regulated by Gi proteins

Answer 9

-Adenylyl cyclase inactivated, no cAMP activated, PKA not activated, no phosphorylation cascade
-M2 muscarinic receptor opened, K+ efflux, hyperpolarisation

Question 10

List receptors linked to Gq proteins

Answer 10

Alpha 1, M1, M3

Question 11

Effectors regulated by Gq proteins

Answer 11

Phospholipase C,
which liberates the second messengers: diacyl- glycerol
(DAG) and inositol triphosphate (IP3):
• DAG activates protein kinase C (PKC) → phosphorylation cascade.
• IPs stimulates Ca+ release from sarcoplasmic reticulum →change in cell activity.

Question 12

List agonists that interact with receptors regulating transcription

Answer 12

Steroid hormones
Estrogen
Progesterone
Thyroid hormones
Vitamin D

Question 13

Mechanism of action of receptors regulating transcription

Answer 13

Steroid hormones, estrogen, progesterone, thyroid hormones and vitamin D enter the target cell and combine with intracellular receptor proteins associated with nuclear chromatin (DNA) to activate or inhibit transcription of the nearby gene. This will modify protein production and cause changes in the structure or function of the target tissue.

Question 14

Are NO receptors extracellular or intracellular?

Answer 14

Intracellular

Question 15

Mechanism of action of NO receptors

Answer 15

Binding of NO triggers an allosteric change in the protein, which in turn, triggers the formation of a “second messenger” within the cell.

Question 16

Most common example for protein NO receptor?

Answer 16

Soluble guanylyl cyclase enzyme, generated cGMP

Question 17

Drugs that activate NO receptors?

Answer 17

Nitrovasodilators
M3 muscarinic agonists (secrete endothelial NO)
Phosphodiesterase inhibitors (result in cGMP formation)

Question 18

Examples for nitrovasodilators?

Answer 18

Nitrites
Nitrates e.g. nitroglycerine and sodium nitroprusside

Question 19

List examples of non-receptor mediated drug mechanisms

Answer 19

• Act on enzymes
• Act on plasma membranes
• Act on subcellular structures
• Acting on genetic apparatus
• Physical action
• Chemical action

Question 20

List drugs that act on enzymes and their effects

Answer 20

• MAO inhibitors inhibit destruction of norepinephrine
• Cholinesterase inhibitors inhibit breaking down of ACH
• Aspirin (COX inhibitor) decreases prostaglandin production

Question 21

List drugs that act on plasma membranes and their effects

Answer 21

• Cardiac glycosides inhibit membrane-bound ATPase.
• Polyene antifungal drugs increase permeability of fungal plasmatic membrane.

Question 22

General effect of drugs acting on plasma membranes?

Answer 22

Affect permeability, transport processes, carrier and enzyme systems

Question 23

List drugs that act on subcellular structures and their effects

Answer 23

Mitochondria: salicylates uncouple oxidative phosphorylation.
Microtubules: Colchicine disrupts microtubules inhibiting mitosis.

Question 24

List drugs that act on genetic apparatus and their effects

Answer 24

• Antibiotics
(e.g. aminoglycosides, chloramphenicol & tetracyclines) inhibit bacterial protein synthesis.
• Anticancer drugs affect DNA synthesis or function.

Question 25

List drugs acting by physical means and their effects

Answer 25

• Demulcents (soothing): bismuth salts coat intestinal mucosa.
• Adsorbents: charcoal adsorbs gases and toxins in intestine.
• Lubricants: liquid paraffin is used in constipation.
• Osmosis: osmotic diuretics.

Question 26

List drugs acting by chemical action and their effects

Answer 26

a. Antacids neutralize HCL in peptic ulcer.
b. Citrates interact with calcium to inhibit blood coagulation.
c. Protamine neutralizes heparin by its positive charge in treatment of heparin overdose.
d. Chelators used in heavy metal poisoning

Question 27

Examples of chelators and the heavy metals they chelate

Answer 27

1. Ethylene diamine tetra acetic acid (EDTA) chelates lead & calcium.
2. Dimercaprol (BAL) chelates arsenic, gold & copper.
3. Penicillamine chelates copper in Wilson’s disease.
4. Deferoxamine chelates iron and is used in iron toxicity.