AJP - Cell Physiology, Vol 255, Issue 5 C633-C640, Copyright © 1988 by American Physiological Society
TRH and BAY K 8644 synergistically stimulate prolactin release but not 45Ca2+ uptake
J. A. Pachter, G. J. Law and P. S. Dannies
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Thyrotropin-releasing hormone (TRH) (1 microM) and the Ca2+-channel agonist
BAY K 8644 (1 microM) each induced transient increases in prolactin
secretion from primary cultures of rat anterior pituitary cells in
perifusion. When BAY K 8644 was added after a TRH-induced secretory peak,
the additional effect of BAY K 8644 on prolactin release was approximately
twofold greater over a 30-min period than the effect of BAY K 8644 on
previously untreated cells. TRH and BAY K 8644 were also synergistic when
added in the opposite order or simultaneously. Substitution of other agents
for BAY K 8644 revealed that only high K+ (40 mM) was at least additive
with TRH in stimulating prolactin secretion; treatment with TRH inhibited,
rather than facilitated, subsequent stimulation of prolactin secretion by
angiotensin II (100 nM) or the ionophore A23187 (20 microM). The
cooperative effect was not specific for TRH because BAY K 8644 also acted
synergistically with angiotensin II or 40 mM K+. In GH4C1 cells, in which
TRH and BAY K 8644 were also synergistic in releasing prolactin,
measurements with the fluorescent indicator indo-1 showed that TRH and BAY
K 8644 could each elevate cytosolic Ca2+ above the level stimulated by the
other. Unexpectedly, TRH was found to inhibit BAY K 8644-stimulated 45Ca2+
uptake in both GH4C1 and primary cultured cells. These results indicate
that BAY K 8644 and TRH synergistically stimulate prolactin secretion by a
mechanism other than a cooperative effect on the activity of
dihydropyridine-sensitive Ca2+ channels.
