Actions and Pathophysiological Roles of Leukotrienes
| Home | | Pharmacology |Chapter: Essential pharmacology : Prostaglandins, Leukotrienes (Eicosanoids) and Platelet Activating Factor
The straight chain lipoxygenase products of arachidonic acid are produced by a more limited number of tissues (LTB4 mainly by neutrophils; LTC4 and LTD4—the cysteinyl LTs—mainly by macrophages), but probably they are pathophysiologically as important as PGs.
ACTIONS AND PATHOPHYSIOLOGICAL ROLES
Leukotrienes
The straight chain
lipoxygenase products of arachidonic acid are produced by a more limited number
of tissues (LTB4 mainly by neutrophils; LTC4 and LTD4—the
cysteinyl LTs—mainly by macrophages), but probably they are pathophysiologically
as important as PGs.
CVS and
blood
LTC4 and LTD4 injected i.v. evoke a brief rise in
BP followed by a more prolonged fall. The fall in BP is not due to
vasodilatation because no relaxant action has been seen on blood vessels. It is
probably a result of coronary constriction induced decrease in cardiac output
and reduction in circulating volume due to increased capillary permeability.
These LTs markedly increase capillary permeability and are more potent than
histamine in causing local edema formation. LTB4 is highly
chemotactic for neutrophils and monocytes; this property is shared by HETE but
not by other LTs. Migration of neutrophils through capillaries and their
clumping at sites of inflammation in tissues is also promoted by LTB4.
Role
LTs are important
mediators of inflammation. They are produced (along with PGs) locally at the
site of injury. While LTC4 and D4 cause exudation of
plasma, LTB4 attracts the inflammatory cells which reinforce the
reaction. 5HPETE and 5HETE may facilitate local release of histamine from mast
cells.
Smooth Muscle
LTC4 and D4 contract most smooth muscles. They
are potent bronchoconstrictors and induce spastic contraction of g.i.t. at low
concentrations.
They
also increase mucus secretion in the airways.
Role
The
cysteinyl LTs (C4 and D4) are
the most important mediators of
human allergic asthma. They are released along with PGs and other autacoids
during AG: AB reaction in the lungs. In comparison to other mediators, they are
more potent and are metabolized slowly in the lungs, exert a long lasting
action. LTs may also be responsible for abdominal colics during systemic
anaphylaxis.
Afferent Nerves
Like PGE2 and I2, the LTB4 also sensitizes afferents carrying pain
impulses— contributes to pain and tenderness of inflammation.
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