Ecosanoid

Eicosanoids


Origin and metabolism. The eicosanoids,

prostaglandins, thromboxane,

prostacyclin, and leukotrienes, are

formed in the organism from arachidonic

acid, a C20 fatty acid with four

double bonds (eicosatetraenoic acid).

Arachidonic acid is a regular constituent

of cell membrane phospholipids; it is

released by phospholipase A2 and forms

the substrate of cyclooxygenases and

lipoxygenases.

Synthesis of prostaglandins (PG),

prostacyclin, and thromboxane proceeds

via intermediary cyclic endoperoxides.

In the case of PG, a cyclopentane

ring forms in the acyl chain. The letters

following PG (D, E, F, G, H, or I) indicate

differences in substitution with hydroxyl

or keto groups; the number subscripts

refer to the number of double

bonds, and the Greek letter designates

the position of the hydroxyl group at C9

(the substance shown is PGF2!). PG are

primarily inactivated by the enzyme 15-

hydroxyprostaglandindehydrogenase.

Inactivation in plasma is very rapid;

during one passage through the lung,

90% of PG circulating in plasma are degraded.

PG are local mediators that attain

biologically effective concentrations

only at their site of formation.

Biological effects. The individual

PG (PGE, PGF, PGI = prostacyclin) possess

different biological effects.

Nociceptors. PG increase sensitivity

of sensory nerve fibers towards ordinary

pain stimuli (p. 194), i.e., at a given

stimulus strength there is an increased

rate of evoked action potentials.

Thermoregulation. PG raise the set

point of hypothalamic (preoptic) thermoregulatory

neurons; body temperature

increases (fever).

Vascular smooth muscle. PGE2

and PGI2 produce arteriolar vasodilation;

PGF2!, venoconstriction.

Gastric secretion. PG promote the

production of gastric mucus and reduce

the formation of gastric acid (p. 160).

Menstruation. PGF2! is believed to

be responsible for the ischemic necrosis