AJP - Endocrinology and Metabolism, Vol 249, Issue 3 326-E329, Copyright © 1985 by American Physiological Society
Calcium channel agonist BAY k8644 enhances anterior pituitary secretion in rat and monkey
M. J. Cronin, J. M. Anderson, A. D. Rogol, D. R. Koritnik, M. O. Thorner and W. S. Evans
A calcium channel agonist BAY k8644 was applied to anterior pituitary (AP)
cells in vitro. BAY k8644 (0.1-10 microM) stimulated prolactin and growth
hormone (GH) release from monolayer AP cultures; the calcium channel
antagonist D-600 (1-10 microM) completely blocked this effect. By utilizing
a perifusion system, we observed an immediate and sustained amplification
of prolactin (2.9-fold), growth hormone (2.3-fold), and luteinizing hormone
(LH, 1.6-fold) release during the 1-h application of BAY k8644 (3 microM).
A hypophysiotrophic peptide pulse 4 h after the BAY k8644 was removed
confirmed that the cells remained responsive to their natural
secretagogues. In another perifusion study 10-3,000 nM BAY k8644 produced a
graded increase in prolactin release that was maintained over the 30-min
exposure period. Finally, individual primate mammotrophs and somatotrophs
showed a marked enlargement of hemolytic plaque area, an index of hormone
release, 1 h after BAY k8644 (1 microM). We conclude that this synthetic
dihydropyridine enhances the rate of prolactin, GH, and LH release from AP
cells of two species. Because this is the first synthetic calcium channel
agonist, structure-function studies characterizing calcium channel
activation and exocytosis are now feasible.
