Lab 3 Cellular Signaling and Drug Receptors PDF
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The British University in Egypt
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This document provides an outline and details of cellular signaling and drug receptors, an elective course at the British University in Egypt. It covers topics such as defining cellular receptors and ligands, discussing protein targets for drug binding, exploring the history of the drug receptor concept, and examining drug-receptor interactions and types of drug receptors. The document is also likely part of a practical laboratory exercise as indicated by the "Phospho-protein test" section.
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CELLULAR SIGNALING AND DRUG RECEPTORS Elective course Biochemistry Department Faculty of Pharmacy BUE OUTLINE 1) Define: Cellular receptor, ligands, drug and drug receptor. 2) Protein targets for drug binding. 3) A brief history of the drug receptor conce...
CELLULAR SIGNALING AND DRUG RECEPTORS Elective course Biochemistry Department Faculty of Pharmacy BUE OUTLINE 1) Define: Cellular receptor, ligands, drug and drug receptor. 2) Protein targets for drug binding. 3) A brief history of the drug receptor concept. 4) Drug-receptor interactions and binding. 5) Types of drug receptors. Cellular receptor Cellular macromolecule, or an assembly of macromolecules mainly protein in nature present either inside a cell or on its surface which receive a signal. They are sensing elements in the system of yellow heart light bulb chemical communications that coordinates the function of all different cells in the body. A receptor is analogous to a switch that it has two configurations “ON” and “OFF”. Ligands It is a chemical messenger released by one cell to signal either itself or a different cell. Types of ligands: Hydrophobic ligands: often target internal receptors → capable of passing through the plasma membrane without help such as steroids like cortisol. Hydrophilic ligands: are unable to pass through the cell membrane → must target cell surface receptors such as GABA. Drug A chemical substance that interacts with a biological system to produce a physiologic effect. It is any substance or product that is used for treatment, prevention or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient. All drugs are chemicals but not all chemicals are drugs. Drug receptor A protein macromolecule produced by the body that was designed by nature to interact with an endogenous molecule (ligand), but which will also interact with a drug molecule, if it has the correct chemical structure. Formula: D + R = D-R ------ Drug Response Note: Binding of a drug to the receptor is usually reversible. PROTEIN TARGETS FOR DRUG BINDING ❖Four main kinds of regulatory protein are commonly involved as primary drug targets. 1. Receptors (Insulin → Insulin receptors) 2. Enzymes (methotrexate → dihydrofolate reductase) 3. Carrier molecules (transporters) (SSRIs,TCA → serotonin transporter (SERT)) 4. Ion channels (local anesthetics →voltage-gated Na+ channel (VGSC)) PROTEIN TARGETS FOR DRUG BINDING A brief History of the Drug Receptor Concept The birth of the receptor concept was the outcome of circumstances in the lives of its two founding fathers, the physiologist John Langley (1852-1925), and the immunologist and bacteriologist Paul Ehrlich (1854- 1915). 1948: Ahlquist (1914–1983) showed the differential action of adrenaline and demonstrated its effects on two distinct receptor populations (α- and β- adrenoceptors) and the theory of receptor-mediated drug interactions gained acceptance. That receptor research began to provide a powerful basis for pharmaceutical innovation. Drug-Receptor Interactions ✓ Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. ✓ Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue. High-potency drugs have high affinity, even at low concentrations. Agonists have high affinity and efficacy, leading to maximal tissue response (activates the receptor to generate a cellular reaction). Partial agonists have intermediate efficacy and produce submaximal responses, even with full receptor occupancy. Antagonists compete with endogenous ligands for receptor binding and have negligible efficacy (bind to receptors without causing their activation). Drug-Receptor Binding ✓ Drugs bind to their respective receptor in a variety of ways depending on their characteristics. ▪ Ionic interaction: cation & anion ▪ Hydrogen bonding ▪ Lipophilic interaction ▪ Covalent bond: irreversible Types of drug receptors ❖Four primary receptor families: 1) Ligand Gated Ion Channels. 2) G-Protein Coupled receptors. 3) Enzyme Linked receptors. 4) Nuclear receptors. Tyrosine kinase receptors G Protein-Coupled Receptors Phospho-protein test (Testing presence of phosphoproteins) 5ml protein (Casein) + 5ml (20% NaOH), B.W.B (30 min.), Then cool the lysate.
