Eicosanoids Flashcards
1
Q
Eicosanoids are?
A
Agonists
2
Q
Eicosanoids mediate their effects via?
A
- 7-pass transmembrane receptors
2. Heterotrimeric G-proteins
3
Q
Eicosanoid half-life
A
Very short (seconds to minutes)
4
Q
Why do eicosanoids have limited range of action?
A
Very short half-life
5
Q
Eicosanoid signaling
A
- Paracrine
2. Autocrine
6
Q
Eicosanoids are clinically important because they participate in?
A
- Platelet aggregation
- Inflammation, arthritis, asthma
- GI integrity
- Kidney and liver homeostasis
- Repro (ovulation and parturition)
- Development
7
Q
Eicosanoids are named for being?
A
Derivatives of a 20 (eicos) carbon FA chain
8
Q
4 major classes of eicosanoids
A
- Prostacyclins
- Prostaglandins
- Thromboxanes
- Leukotrienes
9
Q
Subscript number in eicosanoid name indicates?
A
Number of unsaturated bonds in their chemical structure
10
Q
Prostaglandins mediate?
A
All 4 cardinal signs of inflammation
11
Q
4 cardinal signs of inflammation
A
- Rubur
- Tumor (swelling)
- Calor
- Dalor
12
Q
Rubor is caused by?
A
Vasodilation
13
Q
Tumor
A
Swelling via increased vascular permeability
14
Q
Dolor
A
Pain by sensitizing nociceptors
15
Q
Survival factors for GI stem cells are generated by?
A
COX-1
16
Q
Glucocorticoid function
A
Increase blood glucose levels to support brain function
17
Q
Signal for glucocorticoid production
A
ACTH
18
Q
ACTH is released in response to?
A
Stress
19
Q
ACTH stands for?
A
Adenocorticotropic hormone
20
Q
ACTH is released from?
A
Pituitary gland
21
Q
Effect of ACTH on glucose transport and metabolism
A
Inhibits (counteracts insulin)
22
Q
ACTH action in muscle, CT, skin and bone
A
Protein catabolism
23
Q
ACTH action in liver
A
Gluconeogenesis from AAs
24
Q
ACTH suppresses:
A
- Immune-response
2. Inflammation
25
Synthetic glucocorticoids are used to treat?
1. Auto-immune disease
| 3. Inflammatory disease
26
COX-1 is involved in?
1. Platelet aggregation
| 2. Vasoconstriction
27
COX-2 contributes to?
Prevention of unwanted platelet aggregation and vasoconstriction
28
Toxicity of COX-2 inhibitors are associated with?
Inhibition of protective mechanisms
29
Low doses of aspirin block?
COX-1 in platelets without affecting COX-2 in endothelia
30
Healthy endothelial cells express?
COX-2
31
COX-2 in endothelial cells generates?
PGI(2)
32
PGI(2)
1. Prevents platelet activation and aggregation
| 2. Promotes vasodilation via PI-R
33
PI-R stands for?
PGI(2) receptors
34
PI-R signals via?
1. G(s)
2. Adenylyl cyclase (AC)
3. cAMP
4. PKA
35
PI-R activates?
Ca2+-ATPases in ER or CR to keep cytosolic Ca2+ low
36
Low cytosolic Ca2+ in platelets
Prevent shape change and aggregation
37
Low cytosolic Ca2+ in vascular smooth muscle cells
Promotes vasodilation
38
What stimulates COX-1 in destroyed endothelium?
Platelet adhesion to ECM
39
COX-1 in platelets generates?
TXA(2)
40
TXA(2) causes?
1. Platelet activation and aggregation
| 2. Vasoconstriction
41
How does TXA(2) cause platelet activation, aggregation and vasoconstriction?
TP-R
42
TP-R stands for?
TXA(2) receptors
43
TP-R signals?
1. G(q)
2. IP3
3. PLC
44
PLC stands for?
Phospholipase C
45
TP-R signals G(q), PLC and IP3 to?
Release Ca2+ from ER → elevates cytosolic Ca2+
46
High cytosolic Ca2+ in platelet initiates?
Shape changes and aggregation
47
High cytosolic Ca2+ in smooth muscle cells cause?
Vasoconstriction
48
Mast cells in the airway mucosa react to antigen by releasing?
Leukotrienes:
1. LTB(4)
2. LTC(4)
3. LTD(4)
4. LTE(4)
49
LTB(4) does what?
Attracts eosinophils to leave bloodstream and enter airway mucosa
50
Eosinophils are an additional source of?
Leukotrienes
51
LTC(4), LTD(4) and LTE(4) cause?
Asthmatic symptoms
52
Asthmatic symptoms caused by LTC(4), LTD(4) and LTE(4)?
1. Bronchioconstriction
3. Edema
4. Secretion of heavy mucus
53
How do LTC(4), LTD(4) and LTE(4) cause edema?
Increasing vascular permeability
54
Asthmatic symptoms can be a side-effect of?
Cyclooxygenase inhibitors
55
Why can asthmatic symptoms be a side-effect of cyclooxygenase inhibitors?
Shuffling o arachidonic acid metabolism toward 5-lipoxygenase pathway
56
Hormones high during follicular phase
1. Estrogen
2. LH
→ Ovulation
57
Hormones high during luteal phase
1. Progesterone
2. PGF(2alpha)
→ Regression
58
LH stands for?
Luteinizing hormone
59
GnRH stands for?
Gonadotropin releasing hormone
60
GnRH is secreted by?
Hypothalamus
61
GnRH stimulates release of?
1. FSH
2. LH
From pituitary
62
FSH and LH are released from?
Pituitary
63
LH stimulates?
Theca cells of follicle to synthesize androgens
64
2 examples of androgens released by LH stimulus
1. Testosterone
| 2. Androstendione
65
FSH stimulates?
1. Granulosa cells to synthesize estradiol from androgens
| 2. Production of inhibin
66
Inhibin
Reducses FSH release by negative feedback mechanism
67
Estrogen stimulates?
1. Follicular growth
| 2. GnRH secretion
68
LH surge leads to?
1. Ovulation
| 2. Rebuilding of follicle into CL
69
CL synthesizes?
1. Progesterone
| 2. Oxytocin
70
Progesterone
Inhibits secretion of GnRH → inhibits maturation of ovarian follicles
71
PGF(2alpha) causes?
Luteolysis
72
PGF(2alpha) is generated by what in non-pregnant uterus?
1. Estradiol from maturing follicles
| 2. Progesterone and oxytocin from CL
73
Luteolysis does what?
Removes inhibitory effect of progesterone on hypothalamus → promotes re-entry into estrus cycle
74
SAID stands for?
Synthetic glucocorticoids
75
Most common SAID
Prednisolone
76
Phospholipase A(2)
Removes arachidonic acid from membrane lipids
77
SAID blocks?
Phospholipase A(2)
78
COX stands for?
Cyclooxygenase
79
LOX stands for?
Lipoxygenase
80
NSAIDs block?
COX-1 & 2, 5-LOX
81
PGH(2) is generated by?
COX
82
LTA(4) is generated by?
5-LOX
83
COX-1 is precursor for?
1. PGE(2)
2. PGI(2)
3. Thromboxane TXA(2)
84
PGE(2) and PGI(2) role in gastric mucosa
1. Protection
| 2. Anti-apoptoic
85
Thromboxane TXA(2) found in?
Platelets
86
Role of thromboxane TXA(2) in platelets?
1. Platelet aggregation
| 2. Vasoconstriction
87
Molecules in gastric mucosa
Prostaglandins
88
COX-2 is precursor for?
1. PGE(2)
2. PGI(2)
3. PGD(2)
4. PGF(2alpha)
5. Prostacyclin PGI(2)
89
Prostaglandins in gastric mucosa
1. PGE(2)
| 2. PGI(2)
90
Type of molecules in joints and soft tissue
Prostaglandins
91
Prostaglandins in joints and soft tissue
1. PGE(2)
2. PGI(2)
3. PGD(2)
4. PGF(2alpha)
92
Role of prostaglandins in joints and soft tissue
1. Inflammation
| 2. Pain
93
Type of molecule in vascular endothelium
Prostacyclin PGI(2)
94
Role of PGI(2) in vascular endothelium
1. Platelet resting
| 2. Vasodilation
95
Type of molecule in colon cancer
Prostaglandin PGE(2)
96
Role of PGE(2) in colon cancer
1. Protection
| 2. Anti-apoptotic
97
Type of molecule in bovine uterus
Prostaglandin PGF(2alpha)
98
Function of PGF(2alpha) in bovine uterus?
Luteolysis
99
TXA(2) aka?
Thromboxane
100
PGI(2) aka
Prostacyclin
101
5-LOX is precursor for?
Leucotrienes:
1. LTB(4)
2. LTC(4)
3. LTD(4)
4. LTE(4)
102
Leucotrienes are found in?
Airways
103
Role of leucotrienes in airways
1. Bronchioconstriction
| 2. Mucus secretion
