AJP - Cell Physiology, Vol 253, Issue 1 C162-C170, Copyright © 1987 by American Physiological Society
Pituitary Ca2+ channels: blockade by conventional and novel Ca2+ antagonists
J. J. Enyeart, S. S. Sheu and P. M. Hinkle
We have identified several new agents that block Ca2+ channels in the rat
pituitary GH4C1 cell line. These drugs, which include the
diphenylbutylpiperidine antipsychotic pimozide, the calmodulin antagonist
calmidazolium, and the steroidal Na+ channel toxin veratridine, were
compared with several conventional Ca2+ antagonist in 45Ca2+ uptake,
prolactin secretion, and whole cell patch voltage-clamp experiments.
Pimozide, the most potent of these novel Ca2+ antagonists, inhibited
depolarization-dependent 45Ca2+ uptake and prolactin secretion half
maximally at a concentration of 100 nM, whereas calmidazolium and
veratridine produced 50% inhibition at concentrations of 500 nM and 1
microM. In comparison, the three organic Ca2+ antagonists nitrendipine,
verapamil, and diltiazem blocked 45Ca2+ uptake half maximally at
concentrations of 2.5 nM, 1 microM, and 2.5 microM, respectively. All of
the antagonists inhibited Ca2+ uptake and prolactin secretion stimulated by
the dihydropyridine Ca2+ agonist BAY-K 8644 less potently than
KCl-stimulated responses. In patch-clamp experiments, pimozide,
veratridine, and nitrendipine blocked Ca2+ current through the slowly
inactivating Ca2+ channels of GH4C1 cells. These results demonstrate that
Ca2+ channels in an endocrine cell line can be blocked by a variety of
molecules including sodium channel toxins and calmodulin antagonists. The
data extend the pharmacological similarity between Ca2+ channels in
pituitary and other excitable cells and suggest a structural similarity
among several cellular proteins.
