Cyclic AMP-independent inhibition of voltage-sensitive calcium channels by forskolin in PC12 cells.
Forskolin has been used to stimulate adenylyl cyclase. However, we found that forskolin inhibited voltage-sensitive Ca2+ channels (VSCCs) in a cyclic AMP (cAMP)-independent manner in PC12 cells. Ca2+ influx induced by membrane depolarization with 70 mM K+ was inhibited when cells were preincubated with 10 microM forskolin. Almost maximum inhibitory effect on Ca2+ influx without any significant increase in cellular cAMP level was observed in PC12 cells exposed to forskolin for 1 min. In addition, the forskolin effect on Ca2+ influx was not affected by the presence of 2',5'-dideoxyadenosine, an inhibitor of adenylyl cyclase that reduces dramatically forskolin-induced cAMP production. 1,9-Dideoxyforskolin, an inactive analogue of forskolin, also inhibited approximately 80% of Ca2+ influx induced by 70 mM K+ without any increase in cAMP. The data suggest that forskolin and its analogue inhibit VSCCs in PC12 cells and that the inhibition is independent of cAMP generation.
Park
T J
TJ
Department of Life Science, Pohang University of Science and Technology, Korea.
Kim
K T
KT
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000242:Cyclic AMP; D015640:Ion Channel Gating / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D016716:PC12 Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D005576:Colforsin; D000242:Cyclic AMP; C047983:1,9-dideoxyforskolin; D002118:Calcium