Signalling Mechanisms and non receptor mediated mechanisms Flashcards
List 5 signal transduction systems
1- Ion channel receptors
2- Receptors linked to enzymes
3- G protein coupled receptors
4- Receptors regulating transcription
5- NO receptors
List mechanism of ion channel receptors
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.
2 examples of ion channel receptors + ion channels controlled
Nicotinic ACH receptors (Na/K channels)
GABA receptors (Cl receptors)
Explain mechanism of action of RTKs
• 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.
Structure of G proteins
Alpha, Beta and Gamma subunits forming a trimeric structure
Which receptors are linked to Gs proteins?
Beta receptors
Effectors regulated Gs proteins
Activates adenylyl cyclase, leading to cAMP formation, activating PKA and leading to a phosphorylation cascade
List receptors linked to Gi proteins
Alpha 2 receptors
M2 receptors
Effector regulated by Gi proteins
-Adenylyl cyclase inactivated, no cAMP activated, PKA not activated, no phosphorylation cascade
-M2 muscarinic receptor opened, K+ efflux, hyperpolarisation
List receptors linked to Gq proteins
Alpha 1, M1, M3
Effectors regulated by Gq proteins
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.
List agonists that interact with receptors regulating transcription
Steroid hormones
Estrogen
Progesterone
Thyroid hormones
Vitamin D
Mechanism of action of receptors regulating transcription
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.
Are NO receptors extracellular or intracellular?
Intracellular
Mechanism of action of NO receptors
Binding of NO triggers an allosteric change in the protein, which in turn, triggers the formation of a “second messenger” within the cell.
Most common example for protein NO receptor?
Soluble guanylyl cyclase enzyme, generated cGMP
Drugs that activate NO receptors?
Nitrovasodilators
M3 muscarinic agonists (secrete endothelial NO)
Phosphodiesterase inhibitors (result in cGMP formation)
Examples for nitrovasodilators?
Nitrites
Nitrates e.g. nitroglycerine and sodium nitroprusside
List examples of non-receptor mediated drug mechanisms
- Act on enzymes
- Act on plasma membranes
- Act on subcellular structures
- Acting on genetic apparatus
- Physical action
- Chemical action
List drugs that act on enzymes and their effects
- MAO inhibitors inhibit destruction of norepinephrine
- Cholinesterase inhibitors inhibit breaking down of ACH
- Aspirin (COX inhibitor) decreases prostaglandin production
List drugs that act on plasma membranes and their effects
• Cardiac glycosides inhibit membrane-bound ATPase.
• Polyene antifungal drugs increase permeability of fungal plasmatic membrane.
General effect of drugs acting on plasma membranes?
Affect permeability, transport processes, carrier and enzyme systems
List drugs that act on subcellular structures and their effects
Mitochondria: salicylates uncouple oxidative phosphorylation.
Microtubules: Colchicine disrupts microtubules inhibiting mitosis.
List drugs that act on genetic apparatus and their effects
• Antibiotics
(e.g. aminoglycosides, chloramphenicol & tetracyclines) inhibit bacterial protein synthesis.
• Anticancer drugs affect DNA synthesis or function.
List drugs acting by physical means and their effects
• 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.
List drugs acting by chemical action and their effects
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
Examples of chelators and the heavy metals they chelate
- Ethylene diamine tetra acetic acid (EDTA) chelates lead & calcium.
- Dimercaprol (BAL) chelates arsenic, gold & copper.
- Penicillamine chelates copper in Wilson’s disease.
- Deferoxamine chelates iron and is used in iron toxicity.
