Calcium channel agonist BAY k8644 enhances anterior pituitary secretion in rat and monkey.
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.
M J
MJ
Cronin
J M
JM
Anderson
A D
AD
Rogol
D R
DR
Koritnik
M O
MO
Thorner
W S
WS
Evans
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010908:Pituitary Hormones, Anterior; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011388:Prolactin; D007986:Luteinizing Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D009543:Nifedipine