title: Effects of calcium channel activators BAY-K8644 and CGP-28392 on steroidogenesis in granulosa cells of the domestic hen.
abstract: The effects of calcium agonists BAY-K8644 and CGP-28392 on steroidogenesis was examined in chicken granulosa cells in short term incubation. BAY-K8644 (5-500 nM) and low doses of CGP-28392 (1-10 microM) failed to appreciably affect basal and LH-stimulated progesterone production whether tested in calcium free, low (0.05 mM) or high (3 mM) calcium containing medium. However, higher concentrations of CGP-28392 (50-250 microM) inhibited significantly (P less than 0.01) both basal and LH-stimulated steroidogenesis in a dose-related manner independently of extracellular calcium availability. The suppressive effect of CGP-28392 was manifest with submaximally and maximally stimulating LH doses. In additional experiments with non-hormonal agonists such as forskolin, dibutyryl cyclic AMP and kaurenol, BAY-K8644 and low CGP-28392 concentrations were again without effect on steroidogenesis. By comparison, higher CGP-28392 doses suppressed the stimulatory effects of all three agonists dose-dependently. These results demonstrate that, the calcium channel agonists are incapable of inducing a steroidogenic response in chicken granulosa cells. Since BAY-K8644 and CGP-28392 (low dose, 1-10 microM) failed to influence steroidogenesis in the dose range that induced maximal physiologic responses and calcium influx in a variety of cells, it is concluded that chicken granulosa cells lack the type(s) of channels specific for them. Hence the usefulness of BAY-K8644 and CGP-28392 as Ca2+ probes may be tissue-specific. The inhibitory effects of CGP-28392 appear to be non-specific.
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology*; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D011725:Pyridines; D013256:Steroids; D005576:Colforsin; D011374:Progesterone; D003994:Bucladesine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; D007986:Luteinizing Hormone; D002118:Calcium