title: T-type Ca2+ channels are required for adrenocorticotropin-stimulated cortisol production by bovine adrenal zona fasciculata cells.
abstract: The function of low voltage-activated T-type Ca2+ channels in ACTH-stimulated cortisol production by bovine adrenal zona fasciculata cells (AZF) was explored in patch clamp and secretion studies. Nearly all AZF cells expressed only a low voltage-activated T-type Ca2+ current (IT) that was blocked by the diphenylbutylpiperidine (DPBP) Ca2+ antagonists penfluridol and pimozide with IC50S of 0.3 and 0.5 microM, respectively. Dihydropyridine (DHP) Ca2+ antagonists, including nimodipine, nisoldipine, and felodipine, also blocked T-type Ca2+ current with IC50S ranging from 3.5-8.8 microM. Inhibition of IT by DPBP and DHP antagonists was voltage and use dependent. ACTH (1 nM) stimulated large (> 50-fold) increases in cortisol production by AZF cells, which were inhibited by Ca2+ antagonists at concentrations similar to those which blocked IT. Inhibition of cortisol production by Ca2+ antagonists was specific; ACTH-induced insulin-like growth factor-I production by AZF cells was not affected by DPBP antagonists. The L channel-specific DHP Ca2+ agonist (-)Bay K 8644 did not enhance basal or ACTH-stimulated cortisol synthesis. These results demonstrate that functional T-rather than L-type Ca2+ channels are required for ACTH-stimulated cortisol synthesis. They also suggest that these low voltage-activated channels, acting as the primary pathway for Ca2+ entry into AZF cells, couple ACTH-stimulated membrane depolarization to steroid hormone production.
authors.affiliation: Department of Pharmacology, Ohio State University College of Medicine Columbus 43210-1239.
authors.forename: J J
authors.initials: JJ
authors.lastname: Enyeart
authors.forename: B
authors.initials: B
authors.lastname: Mlinar
authors.forename: J A
authors.initials: JA
authors.lastname: Enyeart
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology; D006854:Hydrocortisone / Q000096:biosynthesis* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D008297:Male; D010395:Penfluridol / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D015398:Signal Transduction; D015383:Zona Fasciculata / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010868:Pimozide; D010395:Penfluridol; D007334:Insulin-Like Growth Factor I; C038806:1,4-dihydropyridine; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D002118:Calcium; D006854:Hydrocortisone