Calcium ion as a second messenger for o-nitrophenylsulfenyl-adrenocorticotropin (NPS-ACTH) and ACTH in bovine adrenal steroidogenesis.
o-Nitrophenyl sulfenyl-modified ACTH (NPS-ACTH) stimulated steroidogenesis acutely in bovine fasciculata-reticularis cells without increase in cellular cAMP synthesis. Application of NPS-ACTH to the cultured cells induced Ca2+ signals in individual cells as detected by video-enhanced microscopic fluorescence measurements. The percentage of Ca2+ signaling cells corresponded well with the increase of steroidogenesis induced by NPS-ACTH below 1 nM. Treatment of the cells with nicardipine, a Ca2+ channel blocker, suppressed the Ca2+ signals except for the transient increase just after the addition of NPS-ACTH and also blocked completely the stimulative effect on the steroidogenesis of NPS-ACTH below 1 nM. At a dosage of NPS-ACTH higher than 10 nM, the stimulative effect of steroidogenesis was partly suppressed by nicardipine and also by AA-861, a lipoxygenase inhibitor. The action of NPS-ACTH might be mediated by both Ca2+ and lipoxygenase metabolite(s) of arachidonic acid as dual second messengers. The effect of ACTH in pM range on the steroidogenesis was suppressed completely by the treatment with nicardipine and AA-861 at the same time, indicating that the action was mediated by both Ca2+ and the lipoxygenase metabolite(s) but not by cAMP. cAMP plays a significant role as a second messenger for ACTH action only at ACTH concentrations greater than 10 pM.
Yamazaki
T
T
Faculty of Integrated Arts and Sciences, Hiroshima University, Higashihiroshima, Japan. takey@ipc.hiroshima-u.ac.jp
Kimoto
T
T
Higuchi
K
K
Ohta
Y
Y
Kawato
S
S
Kominami
S
S
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D015290:Second Messenger Systems / Q000502:physiology*; D013256:Steroids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
C024813:ACTH, 2-nitrophenylsulfenyl-; D002121:Calcium Channel Blockers; D016859:Lipoxygenase Inhibitors; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D009529:Nicardipine; D000242:Cyclic AMP