Arachidonate and its metabolites may play an important role in the release of
prolactin. In the present study, the effect of
maitotoxin, a
calcium channel activator, was measured on the release of arachidonate and its metabolites from the
prolactin-secreting 7315a
tumor.
Maitotoxin increased the release of
prolactin, arachidonate,
prostaglandins E2 and F2
alpha (PGE2,
PGF2 alpha) and
leukotriene C4 (
LTC4) from 7315a cells prelabeled with [3H]arachidonate. The magnitude of the increase of
prolactin and arachidonate release was decreased in low-
calcium medium. The release of arachidonate from cellular
phospholipids is necessary for the effect of
maitotoxin on
prolactin release because
quinacrine, an inhibitor of arachidonate hydrolysis from
phospholipids, blocked the
maitotoxin-induced release of
prolactin. The ability of
maitotoxin to induce
prolactin release appears to require metabolic transformation of arachidonate to its metabolites because
BW755c, an inhibitor of the conversion of arachidonate, blocked the
maitotoxin-induced
prolactin release. In particular,
LTC4 may be an important component of the
prolactin release process because
nordihydroguaiaretic acid and
nafazatrom, which block the production of
leukotrienes and other
lipoxygenase-generated products, decreased
LTC4 and
prolactin release without affecting arachidonate,
PGE2 or
PGF2 alpha production. In contrast,
indomethacin, a
prostaglandin synthesis inhibitor, decreased
PGE2 and
PGF2 alpha production without affecting
LTC4 or
prolactin release. These data indicate that release of
LTC4 and
prolactin are closely linked events in 7315a
tumor cells.