Vasodilation and Constriction. PGE 2 and especially PGI 2 (prostacyclin) are powerful,
short-acting vasodilators, probably involved in blood pressure regulation. Prostaglandin
F 2 and TXA 2 , on the other hand, are potent vasoconstrictors.
Blood Platelet Aggregation. Blood platelet aggregation is an all-important mecha-
nism in normal blood-clot (thrombus) formation, and therefore also highly signifi-
cant in the pathophysiology of cardiovascular disease, stroke, coronary occlusion, and
other circulatory catastrophes. Thromboxane A 2 , formed in platelets, promotes their
aggregation, whereas PGI 2 has the opposite effect, just as in their vaso-activity.
It seems that a very efficient homeostatic control system exists: the endoperoxide
PGH 2 , a precursor of both compounds, is converted in the platelets to TXA 2 but is used
to produce PGI 2 in the blood vessel wall, which does not have thromboxane syn-
thetase. Prostacyclin dilates the vessel and increases the cAMP concentration, which
in turn reverses the platelet aggregation caused by TXA 2 (which inhibits adenylate
cyclase).
Oxytocic Activity. The oxytocic activity of prostaglandins is used clinically.
Prostaglandin E 2 can induce labor at term in pregnant women, while PGF 2 and its
methyl ester are used for terminating pregnancies in the second trimester when admin-
istered by the intrauterine (intraamniotic) route. The activity of PGF 2 and its ester is
probably due to a direct effect on uterine muscle, since in late pregnancy progesterone is
already being produced by the placenta rather than by the corpus luteum. In earlier preg-
nancy,the PGF 2 causes abortion by luteolysis and a decreased production of progesterone.
Abortions initiated in this way are safe, but gastrointestinal side effects (vomiting, diarrhea)
are not uncommon.
Other Effects. Other effects of the prostaglandins include bronchodilation by the
PGE series and constriction by PGF2, as well as antiulcer and antisecretory effects of
some synthetic analogs in the stomach. It has been suggested that alcohol facilitates
arachidonic acid release and subsequent PGE 2 synthesis, and is indeed responsible for
hangover headaches. The analgesic tolfenamic acid (8.66) is alleged to have a preven-
tive effect ... hope springs eternal.
8.5.1.3 Prostaglandin Receptors
Prostaglandin receptors have been demonstrated, even if the extent of binding does not
always correlate with physiological activity. Prostaglandin binding sites have been
reported in adipocytes, the corpus luteum, blood platelets, and the uterus, skin, stomach,
and liver. The KDvalues for these vary from 10−^8 to 10−^11 M, indicating a high affinity;
ENDOGENOUS MACROMOLECULES 523