AVS 271 Anatomy and Physiology

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AVS 271 Anatomy and Physiology

• Handout 13
• October 10, 2008
• Endocrinology
• Chapter 12

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Signal Transduction Pathways

• The mechanisms by which binding of a
  chemical messenger (i.e., hormone) to a
  receptor causes specific cellular responses
  to occur

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Receptor Activation

• Binding of the chemical messenger with its
  receptor causes a change in conformation of
  the receptor called activation
• Allosteric modulation
• e.g., neurotransmitter binding to a ligand
  sensitive ion channel
• Always the initial step leading to the
  cells response to the messenger

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Signal Transduction Pathways

• The sequences of events between receptor
  activation and the final cellular
  response(s) to a chemical messenger

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Typical Cellular Responses to Chemical
Messengers

• Changes in
• Permeability, transport properties or
  electrical activity of the plasma membrane
• Metabolism
• Secretory activity
• Cellular proliferation and differentiation
• Contractile activity
• Gene expression (increase or decrease)

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Signal Transduction Pathways Initiated by
Intra Cellular Receptors

• Utilized by lipid soluble messengers
• e.g., steroid hormones
• Receptors are located in the nucleus, and
  are inactive when no messenger is bound to
  them
• Receptor activation leads to altered rates
  (increase or decrease) of gene transcription
  (expression)
• The activated receptor messenger complex
  functions as a transcription factor

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Intra Cellular Receptors
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Signal Transduction Pathways Initiated by
Plasma Membrane Receptors

• Utilized by lipid insoluble messengers
• The chemical messenger is referred to as
  the first messenger
• Second messengers are generally non protein
  substances that enter the cytoplasm or are
  enzymatically generated as a result of
  receptor activation
• Diffuse throughout the cell to transmit
  signals
• Protein kinases
• Enzymes that phosphorylate specific proteins,
  altering protein conformation and / or
  activity

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Classes of Membrane Receptors

• Receptors that function as ion channels
• e.g., neurotransmitter receptors
• Receptors that function as enzymes
  themselves or are linked to enzymes
• Most have protein kinase activity
• Receptors that activate G proteins, which
  in turn act upon effector proteins (ion
  channels or enzymes) in the plasma membrane

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Receptors that function as ion channels
(e.g., neurotransmitters)
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Receptors that function as enzymes (kinases)
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Receptors that activate G Proteins
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Receptors that interact withG Proteins

• Largest class of plasma membrane receptors
• G proteins are bound to the receptor on
  the inner (cytosolic) surface
• When the receptor is activated, a sub
  unit of the G protein dissociates and
  links up with another plasma membrane
  protein (ion channel or enzyme) and alters
  its function (increase or decrease)

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Examples of G Protein Effector Enzymes

• Adenylyl cyclase (adenylate cyclase)
• Second messenger
• cyclic AMP
• Phospholipase C
• Second messengers
• IP3 (inositol trisphosphate)
• DAG (diacylglycerol)

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Cyclic AMP Second Messenger System
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