L. Gandia et al., DIFFERENTIAL-EFFECTS OF FORSKOLIN AND 1,9-DIDEOXY-FORSKOLIN ON NICOTINIC RECEPTOR-INDUCED AND K-INDUCED RESPONSES IN CHROMAFFIN CELLS(), European journal of pharmacology, 329(2-3), 1997, pp. 189-199
The diterpene forskolin inhibits nicotine-evoked chromaffin cell Ca2influx, scinderin redistribution, F-actin disassembly and catecholamin
e secretion in a concentration-dependent (10-50 mu M) fashion. On the
other hand, forskolin showed weak inhibitory effects when the same res
ponses were elicited by K+-induced depolarization. Similar concentrati
ons of 1,9-dideoxy-forskolin, a forskolin analog which does not activa
te adenylate cyclase, blocked very effectively the responses evoked by
either of the two stimuli. Patch-clamp (whole-cell configuration) stu
dies demonstrated that both diterpenes blocked fast and reversibly pea
k and total chromaffin cell nicotinic acetylcholine receptor currents,
effects not mediated through adenylate cyclase activation. Moreover,
both forskolin and 1,9-dideoxy-forskolin exhibited Ca2+ channel blocki
ng properties. However, 1,9-dideoxy-forskolin was more potent than for
skolin as a Ca2+ channel blocker. Furthermore, 1,9-dideoxy-forskolin w
as also more potent than forskolin as a nicotinic acetylcholine recept
or and Ca2+ channel blocker and it was mon potent as a nicotinic acety
lcholine receptor blocker than Ca2+ channel blocker. The results showe
d powerful cAMP-independent effects of the diterpenes and suggest caut
ion in interpretation of cAMP effects on chromaffin cells when its cel
lular levels are modified by forskolin. (C) 1997 Elsevier Science B.V.