Cell Signaling and Endocrine Regulation PDF

Topic 4:Cell Signaling and Endocrine Regulation  Cellular Communication – Everything an animal does involves communication among cells Example: moving, digesting food – Cell signaling – communication between cells Signaling cell sends a signal (usually a chemical) Target cell...

Topic 4:Cell Signaling and Endocrine Regulation  Cellular Communication – Everything an animal does involves communication among cells Example: moving, digesting food – Cell signaling – communication between cells Signaling cell sends a signal (usually a chemical) Target cell receives the signal and responds to it  Types of Cell Signaling – Direct Signaling cell and target cell connected by gap junctions Signal passed directly from one cell to another – Indirect Signaling cell releases chemical messenger Chemical messenger carried in extracellular fluid – Some may be secreted into environment Chemical messenger binds to a receptor on target cell Activation of signal transduction pathway Response in target cell Indirect Signaling Over Short Distance – Short distance Paracrine – Chemical messenger diffuses to nearby cell Autocrine – Chemical message diffuses back to signaling cell  Indirect Signaling Over Long Distance Long distances – Endocrine System Chemical messenger (hormone) transported by circulatory system – Nervous System Electrical signal travels along a neuron and chemical messenger (neurotransmitter) is released Types of Cell Signaling Figure 3.1 Glands Figure 3.3  Direct Signaling – Gap junctions Specialized protein complexes create an aqueous pore between adjacent cells Movement of ions between cells Changes in membrane potential Chemical messengers can travel through the gap junction – Example: cAMP Opening and closing of gap junction can be regulated Gap Junction Figure 3.2  Indirect Signaling – Three steps Release of chemical messenger from signaling cell (gland) Transport of messenger through extracellular environment to target cell Communication of signal to target cell – Systems for indirect signaling have similarities and differences  Chemical Messengers – Six classes of chemical messengers Peptides Steroids Amines Gases – Structure of chemical messenger (especially hydrophilic vs. hydrophobic) affects signaling mechanism Indirect Signaling Table 3.2  Peptide/Protein Hormones – 2-200 amino acids long – Synthesized on the rough ER Often as larger preprohormones – Stored in vesicles Prohormones – Secreted by exocytosis  Peptide/Protein Hormones – Hydrophilic Soluble in aqueous solutions Travel to target cell dissolved in extracellular fluid – Bind to transmembrane receptors Signal transduction – Rapid effects on target cell Synthesis & Secretion of Peptide Hormones Figure 3.4 Synthesis & Secretion of AVP Figure 3.5 Transmembrane Receptor Figure 3.6  Steroid Hormones – Derived from cholesterol – Synthesized by smooth ER or mitochondria – Three classes of steroid hormones Mineralocorticoids – Electrolyte balance Glucocorticoides – Stress hormones Reproductive hormones – Regulate sex-specific characteristics Synthesis of Steroid Hormones Figure 3.7  Steroid Hormones – Hydrophobic Can diffuse through plasma membrane Cannot be stored in the cell Must be synthesized on demand Transported to target cell by carrier proteins – Example: albumin – Slow effects on target cell (gene transcription) Stress hormone cortisol has rapid non-genomic effects  Steroid Hormones Figure 3.8  Amine Hormones – Chemicals that possess amine group (–NH2) Example: acetylcholine, catecholamines (dopamine, norepinephrine, epinephrine), serotonin, melatonin, histamine, thyroid hormones Sometimes called biogenic amines – Some true hormones, some neurotransmitters, some both – Most hydrophilic Thyroid hormones are hydrophobic – Diverse effects Biogenic Amines Don’t memorize this  Other Chemical Messengers – Gases Most act as paracrines – Example: nitric oxide (NO), carbon monoxide The Role of Nitric Oxide (NO) Figure 16-11a Essential Cell Biology (© Garland Science 2010) Figure 16-11b Essential Cell Biology (© Garland Science 2010) NO Signal Transduction Pathway  Ligand-Receptor Interactions – Ligand-receptor interactions are specific Only the correctly shaped ligand (natural ligand) can bind to the receptor – Ligand mimics Agonists – activate receptors Antagonists – block receptors Many ligand mimics act as drugs or poisons Ligand-Receptor Interactions Figure 3.11  Types of Receptors – Intracellular Bind to hydrophobic ligands – Transmembrane receptors Located in cell plasma memberane Interact with hyrdrophilic messengers  Types of Transmembrane Receptors – Ligand-gated ion channels Lead to changes in membrane potential – Receptor-enzymes Lead to changes in intracellular enzyme activity – G-protein-coupled Activation of membrane-bound G-proteins Lead to changes in cell activities Types of Receptors Figure 3.16  Intracellular Receptors – Ligand diffuses across cell membrane – Binds to receptor in cytoplasm or nucleus – L-R complex binds to specific DNA sequences – Regulates the transcription of target genes increases or decreases production of specific mRNA Intracellular Receptors Figure 3.17  Ligand-Gated Ion Channels – Ligand binds to transmembrane receptor – Receptor changes shape opening a channel – Ions diffuse across membrane – Ions move “down” their electrochemical gradient – Movement of ions changes membrane potential Ligand-Gated Ion Channels Figure 3.19  Receptor Enzymes – Ligand binds to transmembrane receptor – Catalytic domain of receptor starts a phosphorylation cascade – Phosphorylation of specific intracellular proteins Receptor Enzymes Figure 3.20 G-Protein-Coupled Receptors – Ligand binds to transmembrane receptor – Receptor interacts with intracellular G-proteins Named for their ability to bind guanosine nucleotides – Subunits of G-protein dissociate Some subunits activate ion channels – Changes in membrane potential – Changes in intracellular ion concentrations Some subunits activate amplifier enzymes – Formation of second messengers G-Protein-coupled Receptors :Direct Interaction with Ion Channels Extracellular    Intracellular GDP GTP G-Protein-Coupled Receptors Figure 3.25 G-Protein-coupled Receptors: The Second Messenger cyclic AMP Adenylyl   Cyclase   GDP GTP ATP Cyclic AMP Protein Kinase A Enzymes Ion Channels Membrane Transport Cytoskeleton Proteins Cellular Response Summary of G-Protein Activation & Inactivation Cycle Inactive Active G+ GTP G+ GDP GDP GTP   GTP e as  TP G GDP Activates 2nd Messenger Enzymes  Endocrine Regulation Hypothalamus integrates nervous and endocrine regulation regulates activity of pituitary gland produces neurohormones released by posterior lobe of pituitary  Pituitary Hormones – Pituitary gland secretes many hormones – Two distinct anatomic sections: Anterior pituitary (adenohypophysis) Posterior pituitary (neurohypophysis)  Anterior Pituitary Hypothalamus synthesizes and secretes neurohormones  Hypothalamic-pituitary portal system  Anterior pituitary releases hormones Anterior Pituitary Figure 3.30 Hypothalamus and Anterior Pituitary Figure 3.31  Homeostatic Imbalances of the Pituitary Growth Hormone Hypersecretion In youths In adults Growth Hormone Hyposecretion Fig. 48-10b, p. 1041  Posterior Pituitary – Extension of the hypothalamus Neurons that originate in hypothalamus terminate in posterior pituitary oxytocin and vasopressin (ADH) synthesized in hypothalamus and travel in vesicles down axons to posterior pituitary – First-order endocrine pathway Hypothalamus receives sensory input Hypothalamus serves as integrating center Posterior Pituitary Figure 3.29  Constitutive Activation of Aquaporin Genes in the Collecting Duct by ADH Antidiuretic Hormone Water Collecting Duct Lumen Basal Surface Apical Surface  Aquaporin Channels in Adenylyl Vesicular membranes Cyclase Collecting Duct Lumen G-Protein ADH Receptor Apical Basal Surface Surface  P AT MP cA  AT MP P cA PKA  P AT MP cA PKA  P AT MP cA PKA  P AT MP cA PKA