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RECEPTOR concept : 

RECEPTOR concept Surya Narayana Parichha M.PHARM- II nd SEM Department of Chemistry Govt. College of Pharmacy, A ’ bad.


INTRODUCTION Receptor concept was first formulated by Jhon langley in 1878. The term receptor was first introduced by Paul Ehrlich in 1907. It is defined as the sensing elements in system of chemical communication that co-ordinates the function of all different cell in the body. It situated inside or at surface of effecter cell.

Receptor=receiver : 

Receptor=receiver Receptor – a molecule inside/outside of a cell that a drug binds to and uses to produce its effect. Think of a receptor as a receiver in a football game. The receptor receives drugs in the same fashion as a receiver catches a pass from the quarterback.

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Receptors are very specific as to what substances will attach to them and cause a reaction. If the receptor is a different shape then there will be no reaction. These are regulatory macromolucles,proteinious in nature.

Receptor site theories : 

Receptor site theories Occupancy theory Rate theory Induced fit theory Macromolecular perturbation theory Activation aggregation theory

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The occupancy theory: The more receptors sites occupied by ligand, the stronger responce The rate theory: The more ligand-receptor interact / unit time, the stronger responce The induced-fit theory: The macromolecular pertubation theory: (induced fit + rate theory)

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The activation -agregation theory: Always dynamic equilibr.

drug –receptor interaction terms : 

drug –receptor interaction terms Agonist Inverse agonist Antagonist Partial agonist Ligand

Agonists = action : 

Agonists = action Agonist=a molecule that attaches to a receptor and elicits a response similar to that of the physiological signal molecule. Think of agonists as your body’s own chemical teammates

Antagonist = Against : 

Antagonist = Against Antagonist- a molecule that acts against and blocks an action of an agonist Doesn’t have any effect of its own. Think of an antagonist as the opposing teams defense

Contd……. : 

Contd……. Inverse agonist: an agent which activates a receptor to produce an effect in the opposite direction to that of the agonist. Partial agonist: an agent which activates a receptor to produce sub maximal effect but antagonizes the action of a full agonist. Ligand: any molecule which attaches selectively to particular receptors or sites.

Drug-receptor interactions : 

Drug-receptor interactions Most drug-receptor interactions -reversible -weak chemical bonds Irreversible drug-receptor interactions -not common -strong chemical bonds (covalent) -e.g. anti-tumour drug

Contd…. : 

Contd…. Types of interactions Covalent Electrostatic Hydrogen Dipole-dipole and ion dipole Hydrophobic Van der waals Decreasing bond strength

How does the Binding Site Change Shape? : 

How does the Binding Site Change Shape? Before – Intermolecular bonds not optimum length for maximum binding strength After – Intermolecular bond lengths optimised

Main Types of Receptors : 


Ion Channel Receptors : 

Ion Channel Receptors Receptor protein is part of an ion channel protein complex. The receptor is usually a pentameric protein. Receptor binds a messenger leading to an induced fit. Ion channel is opened or closed. Ion channels are specific for specific ions (Na+, Ca2+, Cl-, K+). Ions flow across cell membrane down concentration gradient. EX-nicotinic Ach receptor,GABAA receptors.

Ion Channel Receptors : 

Ion Channel Receptors

Ion Channel Receptors : 

Ion Channel Receptors Transmembrane Proteins TM2 of each protein subunit ‘lines’ the central pore

Gating : 

Gating Five glycoprotein subunits traversing cell membrane Change in memebrene potential or Ionic concentration Cellular effects (milisec)

Contd…. : 

Contd…. Chemical messenger binds to receptor binding site Induced fit results in further conformational changes TM2 segments rotate to open central pore

G protein coupled receptors : 

G protein coupled receptors They called G-proteins because of their interaction with guanine nucleotide GTP and GDP. It consist of 3 subunits alpha, beta and gamma Molecular Structure. They have characteristic 7 transmembrance alpha helices similar to ion channels. classification

The G Protein Activation/Inactivation Cycle : 

The G Protein Activation/Inactivation Cycle

Enzyme linked receptors : 

Enzyme linked receptors Agonist binding site and the catalytic site lies respectively on the outer and inner surface of plasma membrane. Two major subgroups are 1)those that have intrinsic activity. 2)those that lack intrinsic activity.

Receptor tyrosine kinase (RTK) : 

Receptor tyrosine kinase (RTK) Several receptors involved in growth control and differentiation have intrinsic tyrosine kinase activity (e.g., insulin, EGF) Binding ligand to receptor leads to receptor phosphorylation and activation of a cascade of protein kinases phosphorylation of transcription factors activates (inactivates) gene transcription

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Extracellular N-terminal chain Intracellular C-terminal chain Tyrosine kinase-linked receptors

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Reaction catalysed by tyrosine kinase

Jak-stat pathway : 

Jak-stat pathway Hormone-receptor interaction (e.g., growth hormone, cytokines) activates cytoplasmic tyrosine kinase (e.g., JAK1) Tyrosine kinases phosphorylate proteins that dock with other proteins via SH2 domains (bind to phosphotyrosines) STAT binds phosphorylated receptor, becomes phosphorylated, dimerizes, translocates to nucleus, binds specific DNA elements, regulates transcription

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Intracellular receptors Chemical messengers must cross cell membrane Chemical messengers must be hydrophobic Example-steroids and steroid receptors Zinc fingers contain Cys residues (SH) Allow S-Zn interactions

Intracellular Receptors : 

Intracellular Receptors Eg-Steroid receptors - Ligands that are sufficiently soluble to cross the plasma membrane exert their actions by binding to a group of intracellular proteins called the steroid receptor superfamily. Activation of these receptors results in increased transcription of specific genes within the target cells.

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Intracellular receptor Mechanism 4. Binds co-activator protein 7. Protein synthesis activated or inhibited

References : 

References Moroney, A. (2007). Drug-Receptor Interactions. Retrieved September 7, 2008, from Merck web site: Mosby. Mosby's Dictionary of Medicine, Nursing & Health Professions, 7th Edition. Rhodes, M. (2008). Parkinson's Disease Health Center . Retrieved September 7, 2008, from WebMD: Silverthorn, Dee Unglaub,(2007). Human physiology: An integrated approach (forth edition).Austin:Pearson

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