RECEPTORS

RECEPTORS

 

 

 

 

CONTENTS

1- ENZYME-LINKED RECEPTORS
2- LIGAND GATED ION CHANNELS
3- VOLTAGE GATED ION CHANNELS
4- G PROTEIN COUPLED RECEPTORS
5- NUCLEAR RECEPTOR


 

 

 

 

ENZYME-LINKED RECEPTORS

 

These receptors are themselves enzymatic proteins. The agonist binding site lies on the outer, while the catalytic site lies on the inner face of the plasma membrane. These two domains are interconnected through a single trans- membrane stretch of peptide chain.
Most Enzyme-Linked receptors have tyrosine kinase as the enzyme. e.g. Insulin, epidermal growth factor, platelet derived growth factor & certain interleukins. The intracellular events are triggered by phosphorylation of relevant proteins. The receptor itself gets autophosphorylated on tyrosine residues which promote association of several receptor molecules, organizing the complex signaling mechanisms.

 

LIGAND GATED ION CHANNELS

They regulate the flow of ions across the membranes. Ligand binds and regulates their activity. They are fast acting receptors, respond in sub-milliseconds.
Natural ligands include Ach, Serotonin, GABA & Glutamate.
Neurotransmitter binds to the receptor, altering its concentration to open or close the channel to the flow of Na+, K+, Cl- or Ca++ ions across the membrane.
These receptors mediate neurotransmission, cardiac conduction and muscle contraction.


 


VOLTAGE GATED ION CHANNELS

They transport ions across the membrane and are regulated by the electrical potential difference near the channel. Some are composed in a way that they have a central pore through which ions travel down their electrochemical gradients.
Change in potential induces a conformational change in the channel, it opens admitting the ion influx or efflux to occur across the membrane down the electrochemical gradient.
Example include Na+ and K+ Voltage gated channels
They play role in the generation and propagation of nerve impulse across the membrane.

 


 
G PROTEIN COUPLED RECEPTORS

 
These are a large family of cell membrane receptors which are linked to the effector through one or more GTP-activated proteins.
These receptors comprise a α helical peptide which has seven membrane spanning regions.
The extracellular domain contains a ligand binding area, intracellularly, these are linked to a G protein (Gs,Gq,Gi) having 3 subunits α,β,ϒ, that binds GTP.
Binding of ligand to receptor activates the G protein, which releases GDP & binds GTP.
ADENYLYL CYCLASE (c AMP) PATHWAY
Turned on by Gsà activation of Adenylyl Cyclase àintracellular accumulation of
c AMP à increased Ca++ influx and enzyme activity

 

 
PHOSPHOLIPASE C (IP3-DAG) PATHWAY

Turned on by Gq à activation of Phospholipase C à Generation of IP3 & DAG à

Increased intracellular Ca++ and protein kinase activity

 



NUCLEAR RECEPTOR

 
These receptors work with other proteins to regulate the expression of specific genes.
Ligands include thyroid hormone, heme, cholesterol, Vitamin A & D
Ligand binding to the receptors à translocation from cytoplasm to cell nucleus à binding to nuclear hormone response elementsà resulting in up regulation or down regulation of gene expression
There are 48 known human nuclear receptors, e.g. Thyroid hormone receptor, Retinoic acid receptor, Estrogen receptor