Receptors

Front 1

Receptor: 5HT1A

Back 1

Secondary Messenger: Decrease Cyclic AMP

Net Channel Effects: Increase K

Front 2

Receptor: 5HT1B

Back 2

Secondary Messenger: Decrease Cyclic AMP

Net Channel Effects: ---

Front 3

Receptor: 5HT1D

Back 3

Secondary Messenger: Decrease Cyclic AMP

Net Channel Effects: Decrease K

Front 4

Receptor: 5HT2A

Back 4

Secondary Messenger: Increase IP3, DAG

Net Channel Effects: Decrease K

Front 5

Receptor: 5HT2C

Back 5

Secondary Messenger: Increase IP3, DAG

Net Channel Effects: ---

Front 6

Receptor: 5HT3

Back 6

Secondary Messenger: Not G-protein Coupled [Ligand-Gated Ion Channel]

Net Channel Effects: Increase Na

Front 7

Receptor: 5HT4

Back 7

Secondary Messenger: Increase Cyclic AMP

Net Channel Effects: ---

Front 8

Amino Acid: Glutamate

Receptor: Metabotropic

Back 8

Secondary Messenger: Increase IP3, DAG or Decrease Cyclic AMP

Net Channel Effects: ----

Front 9

Amino Acid: Glutamate

Receptor: Ionotropic

Back 9

Secondary Messenger:

Net Channel Effects:

Front 10

Amino Acid: Glutamate

Receptor: AMPA, Kainate

Back 10

Secondary Messenger: -----

Net Channel Effects: Increase Na, K

Front 11

Amino Acid: Glutamate

Receptor: NMDA

Back 11

Second Messenger: -----

Net Channel Effects: Increase Na, K, Ca [Main ion it allows]

Front 12

Amino Acid: GABA

Receptor: GABA-a

Back 12

Second Messenger: ------- [Ion channel]

Net Channel Effects: Increase Cl

Front 13

Amino Acid: GABA

Receptor: GABA-b

Back 13

Second Messenger: Increase IP3, DAG

Net Channel Effects: Increase K, Decrease Ca

Front 14

Gαs: stimulatory

Back 14

Second Messenger: Stimulates production of cyclic AMP from ATP by activating adenylyl cyclase. Increase Protein Kinase A

Front 15

Gαi: inhibitory

Back 15

Second Messenger: Inhibits production of cAMP from ATP by decreasing adenylyl cyclase. Decrease Protein Kinase A.

Gαi > Gαs --- Excess βγ subunits to sequester free Gs

Front 16

Gαq

Back 16

Second Messenger: Increases phospholipase C activity

Front 17

Phosphatidylinositol Pathway

Back 17

Gαq subunit.

PIP2 is acted on by Phospholipase C [which is turned on by Gαq subunit] --> DAG and IP3

What do DAG and IP3 do?

Hint 17

IP3: Water-soluble, binds to a receptor on the membrane of the smooth endoplasmic reticulum and mitochondria. Opens the Calcium Channel which activates Protein Kinase C.

DAG: Remains membrane-bound. Activates Protein Kinase C which will phosphorylate other proteins changing their activity.

Front 18

Protein Kinase C Signaling

Back 18

- Regulation is linked with Phospholipase C activity

- Pathways of PKC signaling include ejaculation, bronchoconstriction, secretion, glucose/glycogen homeostasis

How can Protein Kinase C by turned off?

Hint 18

1) Phosphorylation of DAG

2) Prolonged activation of PKC by phorbol esters

3) Dephosphorylation of PKC

4) Degradation of PKC protein

Front 19

Receptor: Nicotinic

Back 19

Second Messenger: ----

Net Channel Effects: Increase Na, K

Front 20

Receptor: M1, M3, M5 [G-protein coupled]

Back 20

Second Messenger: Increase IP3, DAG

Net Channel Effects: Increase Ca

Front 21

Receptor: M2, M4 [G-protein coupled]

Back 21

Second Messenger: Decrease Cyclic AMP

Net Channel Effects: Increase K

Front 22

Receptor: α1

Back 22

Second Messenger: Increase IP3, DAG

Net Channel Effects: Decrease K

G Proteins: Gαq

Postsynaptic

Front 23

Receptor: α2

Back 23

Second Messenger: Decrease Cyclic AMP and Increase PLC

Net Channel Effects: Increase K, Decrease Ca

G Proteins: Gαi

PRESYNAPTIC***

Front 24

Receptor: β1, β2, β3

Back 24

Second Messenger: Increase Cyclic AMP

Net Channel Effects: ----

Downstream Target: Protein Kinase A --- regulates Ca

G Proteins: Gαs or Gαi [β2 can have component]

Postsynaptic

Front 25

Norepinephrine

Back 25

- α1 and β1 agonist without β2 effect

- Increased Systolic and Diastolic pressure and total peripheral resistance

- Increased stroke volume but no increase in cardiac output

Front 26

Receptor: D1, D5

Back 26

Second Messenger: Increase Cyclic AMP

Net Channel Effects: ----
-
What does D1 do?

Hint 26

- Increase Cyclic AMP

- Increase PIP2 hydrolysis
- Ca mobilization
- PKC activation

Front 27

Receptor: D2

Back 27

Second Messenger: Decrease Cyclic AMP

Net Channel Effects: Increase K, Decrease Ca

What does D2 do?

Hint 27

- Decrease Cyclic AMP

- Increase K currents

- Decrease Voltage-gated Ca currents

Front 28

Receptor: D3, D4

Back 28

Second Messenger: Decrease Cyclic AMP

Net Channel Effects: -----

Front 29

Dopamine

Back 29

- Systemically administered has poor entry into CNS

-Lose Dose Effects
- D1 receptors link to Gαs
- Vasodilation

-Supraphysiologic
- Has β1 stimulatory activity
- Higher doses α1 agonist:
[vasoconstriction]

- Used in treatment of shock

Front 30

Tyrosine Kinase-Receptor Signaling Process?

Back 30

1) Binding of ligand to extracellular binding site of receptor

2) Conformational changes in receptor

3) Activation of kinase activity on cytoplasmic side of receptor

4) Kinase will phosphorylate intracellular mediators and activate common signaling pathways
- PI 3-kinase
- Mitogen-activated protein kinase cascades (MAPK)

Front 31

What happens with the Epidermal Growth Factor Receptor?

Back 31

1) Upon binding of EGF, the receptor converts from its inactive monomeric state to an active dimeric state, in which the two receptor polypeptides bind noncovalently.

2) Cytoplasmic domains become phosphorylated on specific tyrosine residues and their enzymatic activities are activated, catalyzing phosphorylation of substrate proteins (signaling cascade)

Front 32

What are Cetuximab and Panitumumab's role with Epidermal Growth Factor Receptor (EGFR)?

Back 32

- They are monoclonal antibodies that bind to EGFR on the extracellular domain and interfere with EGF binding (antagonist)

- Prevent Downstream signaling

- Cetuximab used for treatment of metastatic colorectal cancer and head and neck cancer

Front 33

Insulin Receptor

Back 33

- Tyrosine Receptor

- α subunit binds insulin

- β subunit transmits a signal from the bound insulin to the cytoplasm (includes ATP binding and tyrosine kinase domains)

- Signal activates autophosphorylation (tyrosine kinase activity) of the cytoplasmic beta domain.

- After insulin receptor is activated, the second messenger, insulin receptor substrate-1 (IRS-1), docks with the insulin receptor and is phosphorylated.

Front 34

What is the IRS-1 Signaling Process?

Back 34

1) The enzyme PI 3-Kinase binds to the phosphorylated IRS-1

2) Catalyzes conversion of the lipid PIP2 to PIP3.

3) PIP3 activates Protein Kinase B (PKB) leading to glycogen synthesis.

4) At the same time, The G Protein Ras binds GTP and stimulates a phosphorylation cascade leading to activation of mitogen-activated protein kinase (MAPK) which enteres the nucleus and alters gene transcription

Front 35

What can PIP2 Signal?

Back 35

1) Phophoslipase C can convert into DAG and IP3

2) PI 3-Kinase can convert into PIP3 which activates Protein Kinase B

Front 36

What are Janus Kinases (JAKS)?

Back 36

- JAK kinases associate with cytokine receptors

- Binding of cytokines to receptors causes a conformational change that activates JAKs

- Once active, JAKs phosphorylate other JAKs and other proteins

- JAKs also phosphorylate STATS*** (signal transducers and activators of transcription) which are transcription factors that regulate immune function and angiogenesis.

Front 37

What is the JAK-STAT signaling pathway?

Back 37

1) Cytokine binds to receptor

2) JAKs cross phosphorylate each other on tyrosines and activate

3) STATs dock on phosphotysines, and JAKs phosphorylate them.

4) STATs dissociate from receptor and dimerize

5) Dimer enters nuclear and begins transcription

Front 38

What is the Arachidonic Acid Pathway?

Back 38

- Arachidonic Acid is a 2nd messenger created from DAG by diacylglycerol lipase or from a free phospholipid by phospholipase A2 (PLA2)

- Acts as a lipid signaling molecule and is a precursor of eicosanoids.

- Involved in inflammatory response.

Front 39

How does cell maintain Low Calcium concentration levels in cytoplasm?

Back 39

1) Na/Ca exchange (at cell membrane)

2) Ca pump (at cell membrane)

3) Ca pump (in smooth endoplasmic reticulum)

4) Ca binding molecule (cytoplasm)

5) Ca importer (into mitochondria)

Front 40

What pathway is Ca-Calmodulin-Dependent Protein Kinase (CaM) formed from?

Back 40

- PIP2 -> IP3 -> Ca release -> Calmodulin -> CaM-Kinase

- Targets of CaM include tryptophan and glycogen homeostatis, synapsin, microtubule function, ion channels, and transcription factors