Forskolin activates voltage-dependent Ca2+ channels in bovine but not in rat fasciculata cells.
The action of forskolin on bovine and rat fasciculata cells was examined in freshly prepared cells. Bovine cells show a close parallelism between production of steroids and production of cAMP as a function of the concentration of ACTH up to 10(-8) M. By contrast, forskolin (10(-7)-10(-5) M) causes a similar increase in steroid synthesis but relatively little effect on the production of cAMP. cAMP-dependent protein kinase shows a similar response to ACTH but no response to forskolin in the same range of concentrations. ACTH and forskolin, at submaximal concentrations, cause greater steroid production when added together than when added separately, but the two agents at high concentrations produce the same response whether added together or separately. The inhibitors of voltage-dependent Ca2+ channels inhibit the steroidogenic response to forskolin (IC50 for nifedipine is 0.1 microM and for Py108-068 is 0.4 microM). A Ca2+ channel agonist (BAY K8644) increases the steroidogenic response of bovine adrenal cells to forskolin, but not that of ACTH. Finally, forskolin causes a concentration-dependent uptake of Ca2+ by these cells; in the concentration range of 0.1-10 microM, forskolin caused an increase in [Ca2+] from 185 nM to 345 nM. By contrast, forskolin caused some stimulation of the production of cAMP, but not that of steroids in rat fasciculata cells. It is concluded that in bovine fasciculata cells forskolin activates voltage-dependent Ca2+ channels with a consequent increase in steroid synthesis. This effect is independent of the well known action of forskolin on adenylate cyclase. Rat fasciculata cells, on the other hand, do not possess such Ca2+ channels and do not show a steroidogenic response to forskolin.
Yanagibashi
K
K
Department of Pharmacology, Jikei University School of Medicine, Tokyo, Japan.
Papadopoulos
V
V
Masaki
E
E
Iwaki
T
T
Kawamura
M
M
Hall
P F
PF
D000067956:Adenylyl Cyclase Inhibitors; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004594:Electrophysiology; D051381:Rats; D013256:Steroids / Q000096:biosynthesis
D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013256:Steroids; D005576:Colforsin; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D002118:Calcium