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.
Department of Life Science, Pohang University of Science and Technology, Korea.
T J
TJ
Park
K T
KT
Kim
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