Interaction of dihydropyridine Ca2+ agonist Bay K 8644 with normal and transformed pituitary cells.
The dihydropyridine (DHP) Ca2+ agonist Bay K 8644 produced a dose-dependent increase in 45Ca2+ uptake by GH4C1 rat pituitary tumor cells. For agonist concentrations between 10(-9) and 10(-5) M, the enhanced 45Ca2+ uptake was well correlated with simultaneous increases in prolactin (PRL) secretion. Bay K 8644 combined with depolarizing concentrations of KCl produced more than additive effects on net Ca2+ uptake and hormone release. Nisoldipine, a DHP Ca2+ antagonist, competitively blocked Bay K 8644-stimulated 45Ca2+ uptake. This drug also potently inhibited 45Ca2+ uptake triggered by depolarization with KCl (estimated half-maximal inhibiting concentration: 2 nM). Bay K 8644 enhanced PRL secretion from normal rat pituitaries in culture and in a perifusion system. These results indicate that Bay K 8644 is a potent modulator of voltage-sensitive Ca2+ channels of both normal and transformed pituitary cells. In this respect endocrine cell Ca2+ channels resemble those found in heart, smooth muscle, and neuronal cell bodies.
Enyeart
J J
JJ
Aizawa
T
T
Hinkle
P M
PM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism; D051381:Rats
D007473:Ion Channels; D015737:Nisoldipine; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011388:Prolactin; D009543:Nifedipine; D002118:Calcium