Deck 22: Lipids: the Eicosanoids: Prostaglandins, Leukotrienes, and Thromboxanes

Question 1

You are investigating a novel series 1 prostaglandin inhibitor on the activity of a section of femoral artery in culture. You have shown that the inhibitory compound directly interferes with the action of PGE
1) Which of the following activies is most likely reduced or absent in your organ culture system in the presence of this inhibitor?

A) activation of 5-LOX for leukotriene synthesis
B) enhancement of neutrophil adhesion
C) induction of slow cardiac contraction
D) platelet aggregation and activation
E) relaxation of vascular smooth muscle cells

Answer 1

relaxation of vascular smooth muscle cells

Question 2

Cells isolated from the lungs of experimental mice via alveolar lavage are being studied for their responses to various lipid molecules.
Results indicate that addition of arachidonic acid leads to increased production of PGE2 but that LTA₄ is not detected. Which of the following enzymes is most likely defective explaining the observed results?

A) COX-1
B) 5-LOX
C) LTC₄ synthase
D) prostacylin synthase
E) thromboxane synthase

Answer 2

B
EXPLANATION: LTA₄ is an intermediate in the linear eicosanoid synthesis pathway. The linear pathway is initiated through the action of LOXs of which there are 3 forms: 5-LOX, 12-LOX, and 15-LOX. It is 5-LOX that gives rise to the leukotrienes. Therefore, loss of LTA₄ detection would most likley be due to loss of 5-LOX activity given that arachidonic acid was utilized effectively as a cyclic pathway (PGE₂) substrate.

Question 3

You are studying the effects of a novel compound in a variety of vascular and immune system assays. Your results demonstrate that the compound exhibits actitivies very similar to a previously identified eicosanoid. These activities include inhibition of platelet and leukocyte aggregation, induction of smooth muscle relaxation, decreased proliferation of T cells, decreased lymphocyte migration, and decreased secretion of IL-1a and IL-2. Which of the following eicosanoids exhibits biological activities most closely resembling those of your test compound?

A) LTB₄
B) LTC₄
C) PGE₂
D) PGI₂
E) TXA₂

Answer 3

D
EXPLANATION: Prostacyclin (PGI₂) is primarily synthesized by cardiac and vascular endothelial cells. Activities associated with this eicosanoid include inhibition of platelet and leukocyte aggregation, decreases in T-cell proliferation and lymphocyte migration and secretion of IL-1a and IL-2. Additional activities include smooth muscle relaxation leading to vasodilation.

Question 4

You are examining the effects of an experimental compound on the activities of cultured sections of rat coronary artery. You determine that the compound exerts an effect identical to the natural prostaglandin, PGE₂ indicating that the compound is exerting which of the folllowing activities?

A) enhanced endothelial permeability
B) increased neutrophil adhesion
C) inhibited platelet adhesion
D) smooth muscle contraction
E) smooth muscle relaxation

Question 5

A 71-year old man was admitted to the hospital after getting very dizzy upon rising from the toilet seat. At that time, his pulse was racing and he remembers that his stool looked very different than usual. Over the last 4 or 5 weeks before the incident, the patient self-medicated with highdose ibuprofen TID to control some pain in his hips. What is the mechanism of action for nonsteroidal anti-inflammatory drugs (NSAIDs) to cause gastrointestinal bleeding?

A) they inhibit arachidonic acid synthesis
B) they inhibit bradykinin synthesis
C) they inhibit cyclooxygenase
D) they inhibit histamine synthesis
E) they promote prostaglandin synthesis

Question 6

You are carrying out clinical studies aimed at determining the optimal nutritional requirements for the production of the series-2 prostaglandins. Your studies determine that this production can be met by the daily ingestion of approximately 10 g of which of the following fatty acids?

A) adipic
B) linoleic
C) palmitic
D) stearic
E) suberic

Question 7

In a healthy newborn soon after delivery, there is constriction of the ductus arteriosus. This process is most likely influenced by which of the following changes?

A) decreased serum calcium concentration
B) decreased serum glucose concentration
C) decreased serum prostaglandin concentration
D) increased serum calcium concentration
E) increased venous blood flow

Question 8

A 23-year-old woman has a severe viral respiratory infection. Her temperature is 38.9°C (102°F), but decreases after she takes aspirin. Which of the following is the most likely mechanism of action of aspirin in decreasing the fever?

A) activation of adenylate cyclase
B) blockade of the action of exogenous viral pyrogens
C) inactivation of lipoxygenase
D) inhibition of cyclooxygenase
E) prevention of mast cell degranulation

Question 9

You are examining the effects of an experimental compound on the synthesis of series-2 prostaglandins. You find that addition of the compound to endothelial cells in culture results in the same level of inhibition as that observed for acetylsalicylate. These results indicate that the compound is inhibiting which of the following reactions of prostaglandin synthesis?

A) acetyltransferase reaction
B) desaturation reaction
C) hydrolytic reaction
D) hydroxylation reaction
E) oxygenation reaction