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area before they are broken down. The two main classes of prostaglandin receptors
are nuclear PPAR receptor class (i.e. PPARα, PPARγ and PPAR δ ) and G-coupled
cytoplasmic receptor class (i.e. EP1–4 for PGE 2 ) (Simmons et al. 2004).
9.1.2.2 Thromboxane
Thromboxane is known to be the key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction.
Cyclooxygenase produces thromboxane A 2 via sequential oxygenation of arachidonic acid, and its properties include vasoconstriction and platelet aggregation.
Thromboxane A 2 which is either a potent platelet agonist or a weak agonist has a
significant role in amplifying the response of platelets to more potent agonists. It
exerts its actions via specific G protein-coupled receptors.
9.1.2.3 Leukotrienes
Leukotrienes (LTs) are arachidonic acid derived pro-inflammatory mediators
formed via 5-LOX and contribute to pathophysiological conditions in asthma and
many other disease conditions. They include cysteinyl LTs (LTC 4 , LTD 4 and LTE 4 )
and LTB 4 (Montuschi 2007). CysLT 1 and CysLT 2 are the two receptor subtypes.
Microvascular permeability increases airway and smoothens muscle activity and
airway mucus secretion in asthma by the stimulation of CysLT 1 receptor (Montuschi
et al. 2007). The second family of leukotrienes includes LTB 4 which acts in inflammatory conditions of cystic fibrosis, psoriasis and inflammatory bowel disease.
Nowadays drugs are designed based on both cysteinyl-leukotriene receptor antagonists and leukotriene synthesis inhibitors. Leukotriene formation can be inhibited
by direct 5- LOX inhibitors or through FLAP inhibitor or via receptor antagonist
mechanism.
9.1.3 Anti-inflammatory Mechanism
An important anti-inflammatory mechanism is the inhibition of enzymes producing
eicosanoids. By the action of phospholipase A 2 (PLA 2 ) arachidonic acid is released
from membrane phospholipids through its cleavage, and further, a signal cascade
leads to the production of prostaglandins (PGs) and thromboxane A 2 (TXA 2 ) by
cyclooxygenase (COX) pathway and hydroperoxyeicosatetraenoic acids (HpETEs),
hydroxyeicosatetraenoicacids (HETEs) and leukotrienes via lipoxygenase (LOX)
pathway. Mainly two forms of cyclooxygenase COX 1 and COX 2 are available, and
another variant form COX 3 is also discovered recently. COX 1 is responsible for
normal homeostasis while COX 2 is inducible and expressed during inflammatory
conditions. Leukotrienes are produced by lipoxygenase and different isoforms
of LOX are present. But only 5 and 12-LOX are involved in the inflammatory
response.
C.S. Sharanya and M. Haridas
area before they are broken down. The two main classes of prostaglandin receptors
are nuclear PPAR receptor class (i.e. PPARα, PPARγ and PPAR δ ) and G-coupled
cytoplasmic receptor class (i.e. EP1–4 for PGE 2 ) (Simmons et al. 2004).
9.1.2.2 Thromboxane
Thromboxane is known to be the key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction.
Cyclooxygenase produces thromboxane A 2 via sequential oxygenation of arachidonic acid, and its properties include vasoconstriction and platelet aggregation.
Thromboxane A 2 which is either a potent platelet agonist or a weak agonist has a
significant role in amplifying the response of platelets to more potent agonists. It
exerts its actions via specific G protein-coupled receptors.
9.1.2.3 Leukotrienes
Leukotrienes (LTs) are arachidonic acid derived pro-inflammatory mediators
formed via 5-LOX and contribute to pathophysiological conditions in asthma and
many other disease conditions. They include cysteinyl LTs (LTC 4 , LTD 4 and LTE 4 )
and LTB 4 (Montuschi 2007). CysLT 1 and CysLT 2 are the two receptor subtypes.
Microvascular permeability increases airway and smoothens muscle activity and
airway mucus secretion in asthma by the stimulation of CysLT 1 receptor (Montuschi
et al. 2007). The second family of leukotrienes includes LTB 4 which acts in inflammatory conditions of cystic fibrosis, psoriasis and inflammatory bowel disease.
Nowadays drugs are designed based on both cysteinyl-leukotriene receptor antagonists and leukotriene synthesis inhibitors. Leukotriene formation can be inhibited
by direct 5- LOX inhibitors or through FLAP inhibitor or via receptor antagonist
mechanism.
9.1.3 Anti-inflammatory Mechanism
An important anti-inflammatory mechanism is the inhibition of enzymes producing
eicosanoids. By the action of phospholipase A 2 (PLA 2 ) arachidonic acid is released
from membrane phospholipids through its cleavage, and further, a signal cascade
leads to the production of prostaglandins (PGs) and thromboxane A 2 (TXA 2 ) by
cyclooxygenase (COX) pathway and hydroperoxyeicosatetraenoic acids (HpETEs),
hydroxyeicosatetraenoicacids (HETEs) and leukotrienes via lipoxygenase (LOX)
pathway. Mainly two forms of cyclooxygenase COX 1 and COX 2 are available, and
another variant form COX 3 is also discovered recently. COX 1 is responsible for
normal homeostasis while COX 2 is inducible and expressed during inflammatory
conditions. Leukotrienes are produced by lipoxygenase and different isoforms
of LOX are present. But only 5 and 12-LOX are involved in the inflammatory
response.
C.S. Sharanya and M. Haridas