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Biochem > GPCR Signaling > Flashcards

GPCR Signaling Flashcards

1
Q

Endocrine signaling - what is it? Examples?

A

Hormone from distant tissue enters blood to reach distant target cell; seen in metabolic pathways

Ex) Insulin/glucagon; pituitary gland

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2
Q

Paracrine signaling - what is it and what’s an example?

A

Signaling and responding cells are very close or adjacent.

Ex) Growth factors, smooth muscle relaxation

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3
Q

Autocrine signaling

A

Signaling cell and the responding cell are the same cell

Seen in many proliferating cell types

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4
Q

When is the G<em>a</em> subunit active?

A

Active when bound to GTP

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5
Q

Summarize the GPCR Signaling pathway

A
  1. Ligand binds GPCR, changing its conformation
  2. GPCR activates the trimeric G protein by triggering dissociation of GDP
  3. Ga binds GTP and leaves the receptor to activate an effector
  4. Effector hydrolyzes Ga’s GTP and generates a second messenger.
  5. Second messenger activates some intracellular and downstream signaling pathway while the ianctivated Ga returns to the By subunits at the GPCR
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6
Q

GPCR > Adenylyl cyclase (effector) > ____ > ____

A

GPCR > Adenylyl cyclase (effector) > cAMP (2nd msger) > PKA pathway

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7
Q

GPCR > Guanylyl cyclase (effector) > ____ > ____

A

GPCR > Guanylyl cyclase (effector) > cGMP (2nd msger) > PKG pathway

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8
Q

GPCR > Phospholipase cyclase (effector) > ____ > ____

A

GPCR > Phospholipase C (effector)

> DAG (2nd msger) > PKC pathway

&

> IP3 (2nd msger) > Ca2+ release from ER (also considered a 2nd msger)

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9
Q

B adrenergic receptor vs a adrenergic receptor impact on cAMP

A

B-adrenergic (epinephrine) receptor activates G<em>as</em> to activate adenylyl cyclase and increase cAMP

a-adrenergic receptoractivates Gai to activate adenylyl cyclase anddecrease cAMP

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10
Q

GPCR siganling activates or shuts down a pathway by

A

Stimulating or inhibiting an effector –> increases or decreases the 2nd msger

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11
Q

Example of how different tissues respond differently to the same signal and GPCR pathway - Epinephrine

A

Epinephrine causes metabolism of fats in adipose tissue; breakdown of glycogen in liver and muscle; increases contractile rate in cardiac muscle; and fluid secretion in the intestine

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12
Q

PKA pathway

A
  1. cAMP binds PKA’s regulatory subunits
  2. PKA’s catalytic subunit enter the nucleus to phosphorylate CREB
    1. Can also phoshporylate MAPK to affect changes in gene expression
  3. CREB is a tf that binds to CRE response elements
  4. CREB-binding proteins (CBP)/p300 tf’s bind CREB and associate with transcriptional machinery to mediate transcription of CRE-containing genes
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13
Q

Cholera & diarrhea

A

Maintains G<em>as</em> -> adenylyl cyclase -> cAMP -> PKA -> CFTR channel

Opening the CFTR channel in intestinal epithelial cells causes Cl- to flow into the intestinal lumen and water follows –> Watery diarrhea

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14
Q

Bordatella pertussis & Whooping cough

A

Turns off G<em>ai</em> -> Adenylyl cyclase -> cAMP -> PKA -> CFTR channel

Opening the CFTR channel in the lung causes fluid loss (as mucous secretion) in the lungs, causing whooping cough

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15
Q

What GPCR signaling pathway is involved in normal heart contraction?

A

B-Adrenergic receptor / cAMP / PKA signaling

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16
Q

How does the B-adrenergic/GPCR/cAMP/PKA signaling pathway cause heart contraciton?

A
  1. The PKA pathway causes an intracellular Ca2+ from the sarcoplasmic reticulum into the cytosol.
  2. Increased cytosolic Ca2+ generates systolic muscle contraction
  3. Myofibril efflux of Ca2+ back into the SR causes relaxation
17
Q

Any __crease in the in the relative amplitude or ratio of cytosolic:SR Ca2+ pools weakens subsequent contractions

A

Decrease

18
Q

Decreased muscle contraction (systolic dysfunction) results from __creased B-adrenergic GPCR signaling

A

Increased B-Adrenergic GPCR signaling

Causes impaired Ca2+ release; defective termination of release; and/or defective calcium sequestration (diastolic dysfunction)

19
Q

How does propranolol work?

A

Propranolol is a beta-blocker- it inhibits B-Adrenergic signaling to re-establish the proper cytosolic:SR ratios of Ca2+ stores –> improves cardiac contractile function

20
Q

Smooth msucle relaxation illustrates what type of signaling?

A

Paracrine signaling among endothelial cells lining blood vessels

21
Q

What’s the ligand for smooth muscle relaxation?

A
  1. Acetylcholine activates PLC to generate IP3 and DAG
  2. IP3 causes release of Ca2+
  3. Ca2+ complexes with calmodulin
  4. Calmodulin-Ca2+ activates nitric oxide synthase
  5. Nitric oxide synthase produces NO
  6. NO diffuses to the neighboring smooth msucle cell and activates guanylyl cyclase
  7. Guanylyl cyclase –> cGMP
  8. cGMP activates PKG
  9. PKG causes smooth muscle relaxation and blood vessel dilation
22
Q

How does phospholipase C activate PKC to phosphorylate target proteins?

A
  1. Phospholipase C cleaves PIP2 into DAG and IP3
  2. IP3 releases Ca2+ from the ER
  3. Ca2+ brings PKC to the plasma membrane, where it is activated by DAG

Biochem (28 decks)

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