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Human physiologyCell Cell Communication

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    Figure 6.19-7 ESSENTIALS Simple and Complex Reflex Pathways

    E

    S

    T

    KEY

    Output PathwaysStimulus

    Sensor

    Sensory neuron(input pathway)

    CNS integratingcenter

    Endocrineintegrating center

    Efferent neuron

    Neurotransmitter

    Neurohormone

    Classic hormone

    Target cell (effector)

    Simple EndocrineReflex

    Stimulus

    Response

    E

    T

    Example:Insulin releasewhen bloodglucose increases

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    Figure 6.1-1 ESSENTIALS Communication in the BodyLOCAL COMMUNICATION

    Gap junctionsformdirect cytoplasmicconnections betweenadjacent cells.

    Contact-dependent signalsrequire interaction betweenmembrane molecules ontwo cells.

    Autocrine signalsact on the same cellthat secreted them. Paracrine signalsare secreted by one cell and diffuse to

    adjacent cells.

    Receptor

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    Figure 6.1-2 ESSENTIALS Communication in the BodyLONG-DISTANCE COMMUNICATION

    Endocrine System Nervous System

    Long-distance signaling may be electrical signals passingalong neurons or chemical signals that travel through thecirculatory system.

    Endocrinecell

    Cellwithoutreceptor

    Cellwith

    receptor Targetcell

    No response

    Response

    Blood

    Hormonesare secreted by endocrine glands or cells into theblood. Only target cells with receptors for the hormone respondto the signal.

    Neurohormonesare chemicalsreleased by neurons into the bloodfor action at distant targets.

    Neurotransmittersare chemicals secreted by neurons that diffuseacross a small gap to the target cell.

    No response

    Response

    Response

    Cellwithoutreceptor

    Cellwith

    receptor

    Targetcell

    Blood

    Neuron

    Neuron

    Electricalsignal

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    Figure 6.3 Target cell receptors may be located on the cell surface or inside the cellIntracellular Signal Receptors

    Four Categories of Membrane Receptors

    Cell Membrane Receptors

    Extracellular signalmolecule binds to acell membranereceptor.

    Bindingtriggers

    Rapid cellularresponses

    Receptorin nucleus

    Receptor in cytosol

    Lipophilic signalmolecules diffuse

    through the cellmembrane.

    Binding tocytosolicor nuclearreceptorstriggers

    Slower responsesrelated to changes

    in gene activity

    Channel Receptor Receptor

    ECF

    Extracellularsignal

    molecules

    ICF

    Enzyme G protein

    Cell

    membrane

    Anchorprotein

    Cytoskeleton

    Ligand binding tointegrin receptorsalters the cytoskeleton.

    Integrin receptorG proteincoupled receptorReceptor-enzyme

    Ligand binding to a G proteincoupled receptor opens an ionchannel or alters enzyme activity.

    Ligand binding to areceptor-enzyme activatesan intracellular enzyme.

    Ligand bindingopens or closesthe channel.

    Receptor-channel

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    Figure 6.5a Biological signal transduction (1 of 2)

    Basic Signal Transduction

    Firstmessenger

    Transducer

    Secondmessengersystem

    Targets

    Signalmolecule

    Membranereceptor protein

    Intracellularsignal molecules

    Targetproteins

    binds to

    activates

    alter

    create

    Response Response

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    Figure 6.6c ESSENTIALS Signal Transduction

    Second messenger pathways

    ATP

    GTP

    Membranephospholipids

    Adenylyl cyclase(membrane)

    Guanylyl cyclase(membrane)

    Guanylyl cyclase(cytosol)

    Phospholipase C(membrane)

    GPCR*

    GPCR

    Receptor-enzyme

    Nitric oxide (NO)

    Activates proteinkinases, especially PKA.Binds to ion channels.

    Activates proteinkinases, especially PKG.

    Binds to ion channels.

    Releases Ca2+fromintracellular stores.

    Activates proteinkinase C.

    Binds to calmodulin.Binds to other proteins.

    Phosphorylatesproteins. Alterschannel opening.

    Phosphorylatesproteins.

    Alters channelopening.

    See Ca2+effectsbelow.

    Phosphorylatesproteins.

    Alters enzyme activity.Exocytosis, musclecontraction, cyto-skeleton movement,channel opening.

    *GPCR G proteincoupled receptor. IP3 Inositol trisphosphage. DAG idacylglycerol

    Ca2+

    IP3

    DAG

    cGMP

    cAMP

    Ions

    Lipid-derived*

    Nucleotides

    SECONDMESSENGER MADE FROM

    AMPLIFIERENZYME LINKED TO ACTION EFFECTS

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    Figure 6.7

    Tyrosine Kinase Receptor

    Tyrosine kinase (TK) transfers a phosphate group fromATP to a tyrosine (an amino acid) of a protein.

    Signal molecule bindsto surface receptor

    Tyrosine kinase oncytoplasmic side

    Phosphorylatedprotein

    ADP

    ATP

    ICF

    Protein Protein

    Active binding site

    Cellmembrane

    ECF

    TK

    R

    L

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    Figure 6.8a (1 of 2)

    GPCR-adenylyl Cyclase Signal Transduction and Amplification

    One signalmolecule

    GPCR

    G protein

    ATP

    Adenylyl

    cyclase

    cAMP

    Proteinkinase A

    Phosphorylatedprotein

    Cellresponse

    Using the pattern shown in Fig. 6.6a,create a cascade that includes ATP, cAMP,adenylyl cyclase, a phosphorylatedprotein, and protein kinase A.

    Protein kinase A phosphorylatesother proteins, leading ultimatelyto a cellular response.

    cAMP activates protein kinase A.

    Adenylyl cyclase converts ATP tocyclic AMP.

    G protein turns on adenylyl cyclase,an amplifier enzyme.

    Signal molecule binds to G proteincoupled receptor (GPCR), whichactivates the G protein.

    FIGURE QUESTION

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    !"#$% '()(*+,' -)./-+(0 1234512 3()'(.,2 6',7 *-2)'(-.)

    8$)(5539 7():-2137 -20 ;54),3( 0(*(20(2)(

    GLP-1 = glucagon-likepeptide 1

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    Figure 6.8b (2 of 2)

    GPCR-phospholipase C Signal Transduction

    Signal

    molecule

    ReceptorG protein

    ERCa2+ Ca2+stores

    PLC

    IP3

    PKC

    DAG

    Membrane phospholipid

    Cellularresponse

    Phosphorylatedprotein

    Protein Pi

    KEY

    PLC phospholipase C

    DAG diacylglycerolPKC protein kinase C

    IP3 inositol trisphosphate

    ER endoplasmic reticulum

    Cellmembrane

    Intracellularfluid

    Extracellular

    fluid

    IP3causes releaseof Ca2+fromorganelles, creatinga Ca2+signal.

    DAG activates proteinkinase C (PKC), whichphosphorylatesproteins.

    PLC converts membrane phospho-lipids into diacylglycerol (DAG), whichremains in the membrane, and IP3,which diffuses into the cytoplasm.

    G protein activatesphospholipase C(PLC), an amplifierenzyme.

    Signal moleculeactivates receptorand associatedG protein.

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    Figure 6.10 ESSENTIALS Summary Map of Signal Transduction

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    Figure 6.13

    Target response depends on the target receptor.

    -Receptor Response 2-Receptor Response

    -Receptor 2-Receptor

    Epinephrine -Receptor Epinephrine 2-Receptor

    Vessel constricts.

    Vessel dilates.

    Intestinal

    blood vessel Skeletal muscleblood vessel

    Epinephrine can bind todifferent isoforms of theadrenergic receptor.

    In this example, blood vesselsdilate or constrict dependingon their receptor type.

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    Figure 6.15b Tonic and antagonist control of regulated variables (4 of 6)

    ANTAGONISTIC CONTROL

    Stimulation by sympathetic nerves increases heart rate.Antagonistic controluses different signalsto send a parameter in opposite directions. Inthis example, antagonistic neurons control heartrate: some speed it up, while others slow it down.

    Sympatheticneuron

    Parasympatheticneuron

    Heartbeats

    Heartbeats

    Time (sec)

    Time (sec)

    0 1 2 3

    Stimulation by parasympathetic nerves decreases heart rate.

    What heart rates (in beats/min)are shown on the two ECGtracings?

    FIGURE QUESTION

    0 1 2 3

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    Figure 6.19-1 ESSENTIALS Simple and Complex Reflex PathwaysComplex Neuroendocrine Reflexes Simple EndocrineReflexSimple NeuralReflex NeurohormoneReflexStimulus Stimulus Stimulus Stimulus Stimulus Stimulus

    Sensor

    Sensory

    neuron

    Efferentneuron

    Neuro-transmitter

    Targetcell

    Example:The knee jerk reflex

    Bloodvessel

    Response

    Response

    Response

    Response

    Response

    Neurotransmitter

    Neurohormone

    Endocrinecells

    Hormone

    Hormone #2

    T

    T

    T

    T

    T

    T

    E

    E

    E

    E1

    E2

    Example:Release of breastmilk in responseto suckling

    Example:Insulin secretion inresponse to a signal

    from the brain

    Example:Secretion ofgrowth hormone

    E

    S

    T

    KEY

    Output PathwaysStimulus

    Sensor

    Sensory neuron(input pathway)

    CNS integratingcenter

    Endocrineintegrating center

    Efferent neuron

    Neurotransmitter

    Neurohormone

    Classic hormone

    Target cell (effector)

    Example:This pattern occurswith hormonesreleased by theanterior pituitary.

    Response

    CNS CNS CNS CNS CNS