KIN 292 1st Edition Lecture 12 Outline of Last Lecture I Exam 1 Outline of Current Lecture I 5 1 Mechanisms of Intercellular Communication II 5 2 Chemical Messengers III 5 3 Signal Transduction Mechanisms Current Lecture Chapter 5 Chemical Messengers 5 3 Signal Transduction Messenger binds to receptor One target may have many types of receptors Binding results in a cell response Signal transduction Process of producing a response in the target after messenger binds to receptor Magnitude of Target Response Strength of response depends on three factors Concentration of the messenger ligand Number of receptors per target cell The number of receptors per cell varies and is dynamic Receptor affinity for the messenger Effects of concentration of messenger target cell receptor concentration and affinity on messenger receptor binding Receptor numbers on a cell can change usually for homeostasis purpose is upregulation results in sensitivity to M Ex GLUT4 by insulin or chronic low M s is downregulation results in sensitivity to M These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute Ex Development of tolerance to a drug Messenger receptor binding is brief and reversible Agonists and Antagonists usually drugs Agonist Example histamine see DISCOVERY p 127 Chemical that binds to a receptor Its action mimics the normal response Antagonist Examples Antihistamines such as Benadryl Chemical that binds to a receptor Binding does not result in a response Competes with the normal ligand Response is the opposite of that to an agonist Mechanisms Signal Transduction Intracellular mediated responses Membrane bound receptor mediated responses Channel linked receptors Enzyme linked receptors G protein linked receptors Mechanisms Signal Transduction 1 Intracellular Mediated Response Characteristic of lipophilic ligands Receptors are found in the cytosol or nucleus Cell response is via gene activation General mechanism next slide from picture HRE portion of DNA regulated by hormones Next slide Fig 5 12 for details of dimerization of steroid and thyroid hormones leading to binding Hormone Response Element Mechanisms Signal Transduction 2 Membrane bound receptor mediated responses Response of the target takes one of two forms Movement of ions Phosphorylation of enzymes Overview of mechanisms Channel linked receptors Fast ligand gated channels Enzyme linked receptors G protein coupled receptors GPCRs Channel Linked Receptors Fast ligand gated channels Receptor and channel same protein Action is direct Binding of ligand causes the channel to open or close Change in transport of ions through the channel causes the target response Examples on next 2 slides Figure 5 13 Fast ligand gated channels and the mechanism by which they change the electrical properties of cells Figure 5 14 Fast ligand gated calcium channels Enzyme Linked Receptors Receptor and enzyme same protein Ligand binding activates the enzyme Action is direct Activated enzyme causes the target response Examples Tyrosine kinases and guanylate cyclases Receptor Tyrosine Kinases http www youtube com watch v ObrsQlvPA4 https www youtube com watch v Ia6OjvBazGE Figure 5 15 An enzyme linked receptor G Protein Coupled Receptors G proteins are regulatory proteins G proteins link ECF messenger to Ion channels Amplifier enzymes ECF messenger first messenger The receptor not the ECF messenger binds to guanosine the G in G protein nucleotides G proteins and second messengers cAMP 2nd messenger system http www youtube com watch v gUC7ZQTp34 Phosphatidylinositol 2nd messenger system http www youtube com watch v 2bbBrpgeheY Signal Amplification Small amounts of ligand can cause a huge response in the target Each step recruits more participants Characteristic of second messengers Small amounts of ligand can cause a huge response in the target Each step recruits more participants Characteristic of second messengers Other important 2nd messenger systems that work by signal amplification Remaining slides show additional figures and text to complement the Figure 5 17 The cAMP second messenger system Figure 5 18 The phosphatidylinositol second messenger system Figure 5 16 G proteins may also open ion channels Action of a G protein on a slow ligand gated ion channel G Protein Coupled Receptors Slow ligand gated channels Receptor and channel different proteins Receptor and channel are linked by the G protein Binding of the ligand activates the G protein which activates the channel Action is indirect Change in transport of ions through the channel causes the target response G Protein Linked Receptors Second messengers Intracellular messengers Triggered by the first messenger ligand activating the G protein coupled receptor The receptor activates the G protein The G protein activates the amplifier enzyme The amplifier enzyme activates second messenger production