Chapter 5 Chemical Messengers PDF

Summary

This document presents a detailed overview of chemical messengers, their mechanisms of intercellular communication, and classifications. It discusses different types of chemical messengers, their functions, and features, including their solubility properties, transport, and impact on target cells. This chapter introduces various aspects of signal transduction.

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PowerPoint® Lecture Presentation CHAPTER 5 Chemical Messengers © 2017 Pearson Education, Inc. Chapter Outline 5.1 5.2 5.3 5.4 Mechanisms of Intercellular Communication Chemical Messengers Signal Transduction Mechanisms Long-Distance Communication via the Nervous and Endocrine Systems © 2017...

PowerPoint® Lecture Presentation CHAPTER 5 Chemical Messengers © 2017 Pearson Education, Inc. Chapter Outline 5.1 5.2 5.3 5.4 Mechanisms of Intercellular Communication Chemical Messengers Signal Transduction Mechanisms Long-Distance Communication via the Nervous and Endocrine Systems © 2017 Pearson Education, Inc. 5.1 Mechanisms of Intercellular Communication • General mechanisms • Direct: Gap junctions • Indirect: Chemical messengers © 2017 Pearson Education, Inc. Figure 5.1a Types of intercellular communication. Ions and small molecules Cell 1 Connexon Cell 2 Direct communication through gap junctions © 2017 Pearson Education, Inc. Figure 5.1b Types of intercellular communication. Chemical messenger Secretory cell Communication via chemical messengers © 2017 Pearson Education, Inc. Receptor Target cell Gap Junctions • • • • • Composed of membrane proteins Link the cytosol of two adjacent cells Particle movement between cells acts as a signal Communication is direct Common in smooth and cardiac muscle © 2017 Pearson Education, Inc. 5.2 Chemical Messengers • • • • • The messenger is produced by the source cell The messenger is released, often by secretion The messenger travels to the target cell The target cell has receptors for the messenger Binding of the messenger to the receptor triggers a target cell response • Communication is indirect © 2017 Pearson Education, Inc. Chemical Messenger Classification • Classification by function • Classification by chemical properties • Solubility properties • Chemical class © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. Messenger Classification by Function • Paracrine chemical messenger • Chemical that signals a nearby cell • Example: Histamine, responsible for an inflammation response • Autocrine chemical messenger • A subclass of paracrines • Chemical that signals the same cell that secreted it • Source and target are the same © 2017 Pearson Education, Inc. Figure 5.2a Functional classes of chemical messengers. Secretory cell Paracrine Receptor Target cell (neighboring cell) © 2017 Pearson Education, Inc. Paracrines Messenger Classification by Function • Neurotransmitter • Messenger produced by neurons • Released into the ECF of the synaptic cleft • Examples: Acetylcholine, GABA, serotonin © 2017 Pearson Education, Inc. Figure 5.2b Functional classes of chemical messengers. Secretory cell (presynaptic) Axon terminal Neurotransmitter Synapse Receptor Target cell (postsynaptic) © 2017 Pearson Education, Inc. Neurotransmitters Messenger Classification by Function • Hormone • Messenger produced by endocrine cells • Secreted into the blood via the interstitial fluid • Examples: Insulin, estrogen, thyroxin • Neurohormone • • • • A special class of hormone Messenger produced by neurons Secreted into the blood Examples: Antidiuretic hormone (ADH), oxytocin © 2017 Pearson Education, Inc. Figure 5.2c Functional classes of chemical messengers. Secretory cell (endocrine cell) Hormone Blood vessel Receptor Target cell © 2017 Pearson Education, Inc. Hormones Nontarget cell (no receptors) Chemical Classification of Messengers • Lipophobic ligand • • • • Water soluble; not lipid soluble Does not cross the cell membrane Receptors on the cell membrane General action of target response • Enzyme activation • Membrane permeability changes © 2017 Pearson Education, Inc. Chemical Classification of Messengers • Lipophilic ligand • • • • Lipid soluble; not water soluble Easily crosses the cell membrane Usually intracellular location of receptors General action of target response is via gene activation © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. Chemical Classification of Messengers • Amino acids • Lipophobic • Target cell receptors on the cell membrane • Only four amino acids function as messengers, all as neurotransmitters • Examples: Glutamate, aspartate, glycine, GABA © 2017 Pearson Education, Inc. Chemical Classification of Messengers • Amines • • • • • Most are lipophobic, except thyroid hormones Target receptors on the cell membrane Made or derived from an amino acid Contains an amine group Examples: • • • • • Catecholamines: Made from tyrosine Dopamine, norepinephrine, ephinephrine Thyroid hormones: Made from two tyrosine amino acids Histamine: Made from histidine Serotonin: Made from tryptophan © 2017 Pearson Education, Inc. Chemical Classification of Messengers • Peptide and protein messengers • • • • Most abundant type of ligand Lipophobic Target receptors on the cell membrane Made of chains of amino acids • Peptide ligand (<50 amino acids) • Protein ligand (>50 amino acids) © 2017 Pearson Education, Inc. Chemical Classification of Messengers • Steroid ligands • Lipophilic • All are derived from cholesterol • All steroid messengers (ligands) function as hormones © 2017 Pearson Education, Inc. Messenger Classification by Chemical Class • Eicosanoid ligands • Lipophilic • Intracellular target receptors • Most are derived from arachidonic acid, a cell membrane phospholipid • Examples: Prostaglandins, leukotrienes © 2017 Pearson Education, Inc. Synthesis and Release of Chemical Messengers • Lipophobic ligands • Synthesized on demand • Immediate release from source • Release rate depends on synthesis © 2017 Pearson Education, Inc. Synthesis and Release Characteristics • Lipophobic ligands • Synthesis is independent of demand • Stored in vesicles of the source until needed • Released by exocytosis: Release rate is determined by exocytosis © 2017 Pearson Education, Inc. Amino Acids • Made from glucose • Glutamate, aspartate • Made from 3-phosphoglycerate • Glycine • From glutamate • Glutamic acid decarboxylase → GABA • Synthesized within a neuron • Stored in vesicles until needed • Released by exocytosis © 2017 Pearson Education, Inc. Amines • • • • Produced in the cytosol of the source Stored in vesicles of the source Released by exocytosis The amine produced is determined by which enzymes are present in the source cell © 2017 Pearson Education, Inc. Figure 5.3 Catecholamine synthesis. Cytosol COOH CH2 HO C NH2 Tyrosine H Tyrosine β-hydroxylase OH COOH CH2 HO Catechol group C NH2 L-Dihydroxyphenylalanine (L-dopa) H Dopa decarboxylase OH CH2 HO CH2 NH2 Dopamine Vesicle Dopamine β-hydroxylase OH CH HO CH2 NH2 Norepinephrine OH Phenylethanolamine N-methyl transferase (PNMT) Cytosol OH HO CH OH © 2017 Pearson Education, Inc. CH2 NH CH3 Epinephrine Peptide and Proteins • • • • Formed by cleaving larger proteins Stored in secretory vesicles Released by exocytosis General terminology © 2017 Pearson Education, Inc. Figure 5.4b Peptide synthesis and release. Preprohormone Prohormone Cleaved amino acids Generalized scheme of hormone synthesis © 2017 Pearson Education, Inc. Hormone Cleaved amino acids Figure 5.4a Peptide synthesis and release. Slide 1 Rough endoplasmic reticulum Golgi apparatus mRNA Polypeptide Prepropeptide Propeptide Cleaved amino acids Propeptide Propeptide Secretory vesicle Transport vesicle Smooth endoplasmic reticulum Prepropeptide Propeptide Cleaved amino acids Peptide synthesis © 2017 Pearson Education, Inc. Peptide Peptide Cleaved amino acids Cleaved amino acids Figure 5.4a Peptide synthesis and release. Rough endoplasmic reticulum mRNA Polypeptide Prepropeptide Smooth endoplasmic reticulum Prepropeptide Peptide synthesis © 2017 Pearson Education, Inc. Slide 2 Figure 5.4a Peptide synthesis and release. Slide 3 Rough endoplasmic reticulum Golgi apparatus mRNA Polypeptide Prepropeptide Propeptide Cleaved amino acids Propeptide Transport vesicle Smooth endoplasmic reticulum Prepropeptide Propeptide Cleaved amino acids Peptide synthesis © 2017 Pearson Education, Inc. Propeptide Secretory vesicle Figure 5.4a Peptide synthesis and release. Slide 4 Rough endoplasmic reticulum Golgi apparatus mRNA Polypeptide Prepropeptide Propeptide Cleaved amino acids Propeptide Propeptide Secretory vesicle Transport vesicle Smooth endoplasmic reticulum Prepropeptide Propeptide Cleaved amino acids Peptide synthesis © 2017 Pearson Education, Inc. Peptide Peptide Cleaved amino acids Cleaved amino acids Steroids • Synthesized on demand • Derived from the cholesterol molecule • All steroid ligands are similar © 2017 Pearson Education, Inc. Figure 5.5 Synthetic pathway for steroids. Cholesterol Nonactive intermediate Progesterone Nonactive intermediate Nonactive intermediate Nonactive intermediate Nonactive intermediate Nonactive intermediate Corticosterone Dehydroepiandrosterone Cortisol Aldosterone Androstenedione Testosterone Estrone Dihydrotestosterone Estradiol Estriol © 2017 Pearson Education, Inc. Eicosanoids • • • • Derived from arachidonic acid Arachidonic acid is a membrane phospholipid Synthesized on demand Two major synthetic pathways • Cyclooxygenase pathway • Lipoxygenase pathway © 2017 Pearson Education, Inc. Figure 5.6 Eicosanoid synthesis. Membrane phospholipid Phospholipase A2 COOH Cyclooxygenase pathway © 2017 Pearson Education, Inc. Prostaglandins Prostacyclins Thromboxanes Arachidonic acid Lipoxygenase pathway Leukotrienes Transport of Messengers • Diffusion through interstitial fluid • Source and target are close • Ligand is quickly degraded • Examples: Paracrines, autocrines, neurotransmitters, most cytokines © 2017 Pearson Education, Inc. Transport of Messengers • Bloodborne transport • • • • Source and target are located at a distance Lipophobic ligands dissolve in plasma Lipophilic ligands bind to carrier protein Examples: Hormones, neurohormones, some cytokines © 2017 Pearson Education, Inc. Figure 5.7a Transport of messengers in blood. Endocrine cell Secreted by exocytosis Blood vessel Dissolved messenger Hydrophilic messenger © 2017 Pearson Education, Inc. Figure 5.7b Transport of messengers in blood. Endocrine cell Secreted by diffusion Free hormone (<1%) Bound to carrier proteins (>99%) © 2017 Pearson Education, Inc. Hydrophobic messenger Messenger Transport • Messenger half-life • Time for a chemical to decrease its concentration by half • Concentration of the messenger could be in blood or interstitial fluid © 2017 Pearson Education, Inc. Messenger Transport • Messenger half-life • Messengers dissolved in plasma • Have a relatively short half-life • Example: Half-life of insulin is less than 10 minutes • Messengers bound to plasma protein • Have a relatively long half-life • Example: Half-life of cortisol is 90 minutes © 2017 Pearson Education, Inc. 5.3 Signal Transduction • Messenger binds to receptor • Binding results in a cell response • Signal transduction • Process of producing a response in the target © 2017 Pearson Education, Inc. Receptor Binding • • • • Specificity Binding is brief and reversible Affinity = strength of binding Location of binding • Lipophobic ligands: Cell membrane • Lipophilic ligands: Within cell © 2017 Pearson Education, Inc. Receptor Properties • • • • Specificity One messenger may bind to many receptor types One target may have many types of receptors The number of receptors per cell varies and is dynamic © 2017 Pearson Education, Inc. Figure 5.8 Receptor specificity. Messenger 1 Messenger 2 Receptor C Receptor A Target cell for messenger 2 Target cell for messenger 1 Receptor B © 2017 Pearson Education, Inc. Magnitude of Target Response • Strength of response depends on three factors: • Concentration of the messenger (ligand) • Number of receptors per target cell • Receptor affinity for the messenger © 2017 Pearson Education, Inc. Percentage of receptors bound Figure 5.9 Effect of messenger concentration on messenger-receptor binding. 100 Concentration of messenger [M] © 2017 Pearson Education, Inc. Figure 5.10a Effects of receptor concentration and affinity on messenger-receptor binding. Number of receptors bound 100% 2R bound 100% R bound Concentration of messenger [M] Effects of receptor concentration © 2017 Pearson Education, Inc. Percentage of receptors bound Figure 5.10b Effects of receptor concentration and affinity on messenger-receptor binding. 100 High affinity for messenger Low affinity for messenger 50 Low [M] Higher [M] Concentration of messenger [M] Effects of receptor affinity © 2017 Pearson Education, Inc. Up-regulation • Receptor number increases on the target • May result from too little messenger • Sensitivity to the messenger increases © 2017 Pearson Education, Inc. Down-regulation • • • • Receptor number decreases on the target May result from excess messenger Sensitivity to the messenger decreases Tolerance to the messenger develops © 2017 Pearson Education, Inc. Agonists and Antagonists • Agonist • Chemical that binds to a receptor • Its action mimics the normal response • Antagonist • • • • 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 © 2017 Pearson Education, Inc. Example of Receptor Agonists and Antagonists • β-endorphin: Endogenous opiate • β-endorphin binds to µ opiate receptors, producing analgesia • Morphine: µ receptor agonist • Administration of morphine produces analgesia • Naloxone: µ receptor antagonist • Administration of naloxone blocks morphine- or β-endorphin–produced analgesia • 10× greater affinity for the µ receptor than morphine © 2017 Pearson Education, Inc. Mechanisms: Signal Transduction • Intracellular-mediated responses • Membrane-bound receptor-mediated responses • Channel-linked receptors • Enzyme-linked receptors • G protein–linked receptors © 2017 Pearson Education, Inc. Intracellular-Mediated Response • Characteristic of lipophobic ligands (except thyroid hormones) • Receptors are found in the cytosol or nucleus • Cell response is via gene activation © 2017 Pearson Education, Inc. Figure 5.11 Actions of lipophilic hormones on the target cell. Slide 1 Lipophilic messenger Extracellular fluid Diffusion Nucleus Target cell DNA Cytoplasmic receptor Nuclear receptor Proteins Ribosome mRNA Hormonereceptor complex © 2017 Pearson Education, Inc. Hormone response element (HRE) mRNA Nuclear envelope Nuclear pore Figure 5.11 Actions of lipophilic hormones on the target cell. Lipophilic messenger Slide 2 Extracellular fluid Diffusion Nucleus Target cell Nuclear receptor Nuclear envelope Nuclear pore © 2017 Pearson Education, Inc. Figure 5.11 Actions of lipophilic hormones on the target cell. Lipophilic messenger Slide 3 Extracellular fluid Diffusion Nucleus Cytoplasmic receptor Nuclear receptor Hormonereceptor complex © 2017 Pearson Education, Inc. Target cell Nuclear envelope Nuclear pore Figure 5.11 Actions of lipophilic hormones on the target cell. Slide 4 Lipophilic messenger Extracellular fluid Diffusion Nucleus Target cell DNA Cytoplasmic receptor Nuclear receptor mRNA Hormonereceptor complex © 2017 Pearson Education, Inc. Hormone response element (HRE) Nuclear envelope Nuclear pore Figure 5.11 Actions of lipophilic hormones on the target cell. Slide 5 Lipophilic messenger Extracellular fluid Diffusion Nucleus Target cell DNA Cytoplasmic receptor Nuclear receptor Proteins Ribosome mRNA Hormonereceptor complex © 2017 Pearson Education, Inc. Hormone response element (HRE) mRNA Nuclear envelope Nuclear pore Figure 5.12a Mechanism of action for steroid and thyroid hormones. Steroid hormone Hormone receptor Receptor protein for steroid hormone DNA binding domain DNA Hormone response element Target gene Dimerization Steroid hormone Steroid hormone Transcription mRNA © 2017 Pearson Education, Inc. Figure 5.12b Mechanism of action for steroid and thyroid hormones. RXR receptor TH receptor DNA binding domain DNA binding domain DNA Hormone response element Target gene Dimerization 9-cis-retinoic acid Triiodothyronine Transcription mRNA © 2017 Pearson Education, Inc. Signal Transduction by Membrane-Bound Receptors • Response of the target takes one of two forms: • Movement of ions • Phosphorylation of enzymes • Overview of mechanisms • Channel-linked receptors • Enzyme-linked receptors • G protein–coupled receptors (GPCRs) © 2017 Pearson Education, Inc. 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 © 2017 Pearson Education, Inc. Figure 5.13 Fast ligand-gated channels and the mechanism by which they change the electrical properties of cells. Extracellular fluid Messenger Channel closed Cytosol © 2017 Pearson Education, Inc. Receptor and ion channel Ions (Na+, K+, Cl–) move through open channel Change in electrical properties of cell Figure 5.14 Fast ligand-gated calcium channels. Extracellular fluid Messenger Calcium channel Channel closed Calcium enters cell through open channel As second messenger Change in Muscle Secretion Calmodulin electrical contraction properties of cell Ca-calmodulin Activates enzymes Protein kinase Protein- P Cytosol © 2017 Pearson Education, Inc. Response in cell (muscle contraction, altered metabolism, altered transport) 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 © 2017 Pearson Education, Inc. Figure 5.15 An enzyme-linked receptor. Extracellular fluid Tyrosine kinase receptor (inactive) Cytosol © 2017 Pearson Education, Inc. Protein-Tyr + Tyrosine kinase receptor (active) Protein-Tyr- P + ADP Response in cell (alter metabolism, regulate protein synthesis) 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 © 2017 Pearson Education, Inc. 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 © 2017 Pearson Education, Inc. Figure 5.16 Action of a G protein on a slow ligand-gated ion channel. Extracellular fluid Messenger Receptor α GDP β G protein Cytosol © 2017 Pearson Education, Inc. α γ GTP GDP GTP Ions move in or out of cell Change in electrical properties of cell 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 © 2017 Pearson Education, Inc. Second Messenger Systems • Binding of the first messenger to the receptor leads to production of the second messenger • Involves G proteins • Gi: Activates amplifier enzyme • Gs: Inhibits amplifier enzyme • Purpose is signal amplification © 2017 Pearson Education, Inc. Second Messenger Systems • Types of second messengers • • • • • Cyclic AMP (cAMP) Cyclic GMP (cGMP) Inositol triphosphate (IP3) Diacylglycerol (DAG) Calcium ions © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. Figure 5.17 The cAMP second messenger system. Slide 1 Extracellular fluid Messenger Adenylate cyclase Receptor GDP α α β γ G protein GTP GDP GTP ATP cAMP Activates Protein kinase A Protein + ATP Cytosol © 2017 Pearson Education, Inc. Protein- P + ADP Response in cell Figure 5.17 The cAMP second messenger system. Messenger Receptor GDP α β γ G protein Cytosol © 2017 Pearson Education, Inc. Slide 2 Figure 5.17 The cAMP second messenger system. Slide 3 Extracellular fluid Messenger Adenylate cyclase Receptor GDP α G protein Cytosol © 2017 Pearson Education, Inc. α β γ GTP GDP GTP Figure 5.17 The cAMP second messenger system. Slide 4 Extracellular fluid Messenger Adenylate cyclase Receptor GDP α α β γ G protein GTP GDP GTP cAMP ATP Cytosol © 2017 Pearson Education, Inc. Figure 5.17 The cAMP second messenger system. Slide 5 Extracellular fluid Messenger Adenylate cyclase Receptor GDP α α β γ G protein GTP GDP GTP ATP cAMP Activates Protein kinase A Cytosol © 2017 Pearson Education, Inc. Figure 5.17 The cAMP second messenger system. Slide 6 Extracellular fluid Messenger Adenylate cyclase Receptor GDP α α β γ G protein GTP GDP GTP ATP cAMP Activates Protein kinase A Protein + ATP Cytosol © 2017 Pearson Education, Inc. Protein- P + ADP Response in cell Figure 5.18 The phosphatidylinositol second messenger system. Slide 1 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein GTP PIP2 DAG IP3 GDP GTP ATP + protein ADP + protein- P Calmodulin Lumen of endoplasmic reticulum Protein kinase C Protein kinase Response in cell Response in cell (contraction, secretion) Protein- P Membrane of endoplasmic reticulum © 2017 Pearson Education, Inc. Response in cell (contraction, metabolism, transport) Cytosol Figure 5.18 The phosphatidylinositol second messenger system. Extracellular fluid Messenger Receptor GDP α Slide 2 β γ G protein © 2017 Pearson Education, Inc. Figure 5.18 The phosphatidylinositol second messenger system. Extracellular fluid Messenger Phospholipase C Receptor GDP α Slide 3 α β γ G protein © 2017 Pearson Education, Inc. GTP GDP GTP Figure 5.18 The phosphatidylinositol second messenger system. Slide 4 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein © 2017 Pearson Education, Inc. GTP GDP GTP PIP2 DAG IP3 Figure 5.18 The phosphatidylinositol second messenger system. Slide 5 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein © 2017 Pearson Education, Inc. GTP GDP GTP PIP2 DAG IP3 Protein kinase C Figure 5.18 The phosphatidylinositol second messenger system. Slide 6 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein © 2017 Pearson Education, Inc. GTP GDP GTP PIP2 DAG IP3 Protein kinase C ATP + protein ADP + protein- P Figure 5.18 The phosphatidylinositol second messenger system. Slide 7 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein GTP GDP GTP PIP2 DAG IP3 Protein kinase C ATP + protein ADP + protein- P Response in cell © 2017 Pearson Education, Inc. Figure 5.18 The phosphatidylinositol second messenger system. Slide 8 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein Lumen of endoplasmic reticulum Membrane of endoplasmic reticulum © 2017 Pearson Education, Inc. GTP GDP GTP PIP2 IP3 Figure 5.18 The phosphatidylinositol second messenger system. Slide 9 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein Lumen of endoplasmic reticulum Membrane of endoplasmic reticulum © 2017 Pearson Education, Inc. GTP PIP2 IP3 GDP GTP Response in cell (contraction, secretion) Cytosol Figure 5.18 The phosphatidylinositol second messenger system. Slide 10 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein GTP PIP2 IP3 GDP GTP Calmodulin Lumen of endoplasmic reticulum Membrane of endoplasmic reticulum © 2017 Pearson Education, Inc. Protein kinase Response in cell (contraction, secretion) Cytosol Figure 5.18 The phosphatidylinositol second messenger system. Slide 11 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein GTP PIP2 IP3 GDP GTP Calmodulin Lumen of endoplasmic reticulum Protein kinase Response in cell (contraction, secretion) Protein- P Membrane of endoplasmic reticulum © 2017 Pearson Education, Inc. Response in cell (contraction, metabolism, transport) Cytosol Figure 5.18 The phosphatidylinositol second messenger system. Slide 12 Extracellular fluid Messenger Phospholipase C Receptor GDP α α β γ G protein GTP PIP2 DAG IP3 GDP GTP ATP + protein ADP + protein- P Calmodulin Lumen of endoplasmic reticulum Protein kinase C Protein kinase Response in cell Response in cell (contraction, secretion) Protein- P Membrane of endoplasmic reticulum © 2017 Pearson Education, Inc. Response in cell (contraction, metabolism, transport) Cytosol © 2017 Pearson Education, Inc. Signal Amplification • Small amounts of ligand can cause a huge response in the target • Each step recruits more participants • Characteristic of second messengers © 2017 Pearson Education, Inc. Figure 5.19 Signal amplification, in this case by the second messenger cAMP. Total number of product One messenger binds to one receptor α β γ Several G proteins are activated α α Each G protein activates an Adenylate adenylate cyclase cyclase One messenger molecule 10 10 leads to… Each adenylate cyclase generates hundreds of cAMP molecules 5000 Protein kinase A Each cAMP activates a protein kinase A 5000 Phosphorylated protein Each protein kinase A phosphorylates hundreds of proteins cAMP © 2017 Pearson Education, Inc. 1 2,500,000 phosphorylation of millions of proteins Endocrine Communication • The endocrine target secretes a hormone • The hormone enters the blood • The blood spans the distance to the target © 2017 Pearson Education, Inc. Nervous Communication • Nerve cells can transmit signals • Within neuron via long axons • Between cells via the synapse • Signal in axon = action potentials • Axons via action potentials span the distance to the target © 2017 Pearson Education, Inc. Figure 5.20 Signal transmission in neurons. Neuron Electrical transmission Neurotransmitter Chemical transmission Synapse Target cell © 2017 Pearson Education, Inc. Receptor © 2017 Pearson Education, Inc.

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