The nonpeptide alpha-eudesmol from Juniperus virginiana Linn (Cupressaceae) inhibits omega-agatoxin IVA-sensitive Ca2+ currents and synaptosomal Ca-45(2+) uptake

Recently, the omega-agatoxin IVA (omega-Aga-IVA)-sensitive Ca2+ channel has been demonstrated to play an important role in the physiological neurotran smitter release in mammalian nerve terminals. In this study, we demonstrate that alpha-eudesmol from Juniperus virginiana Linn. (Cupressaceae) inhibit s omega-Aga-IVA-sensitive Ca2+ channels in rat brain synaptosomes and cereb ellar Purkinje cells. Thirty millimolar KCl-induced Ca-45(2+) uptake into t he synaptosomes was inhibited by omega-Aga-IVA but insensitive to omega-con otoxin GVIA (omega-CTX-GVIA, N-type Ca2+ channel blocker) and nicardipine ( L-type Ca2+ channel blocker). We found that alpha-eudesmol concentration-de pendently inhibited the above synaptosomal Ca-45(2+) uptake with an IC50 va lue of 2.6 mu M. Go-treatment with alpha-eudesmol and omega-Aga-IVA did not cause any additive inhibitory effect against the synaptosomal Ca-45(2+) up take. Using the whole-cell patch clamp electrophysiological technique, we f urther demonstrated that alpha-eudesmol concentration-dependently inhibited alpha-Aga-IVA-sensitive Ca2+ channel currents recorded from Purkinje cells with an IC50 value of 3.6 mu M. The current-voltage relationship of the om ega-Aga-IVA-sensitive Ca2+ channel currents was not changed by alpha-eudesm ol. On the other hand, alpha-eudesmol also displayed an inhibitory effect o n N-type Ca2+ channel currents recorded from differentiated NG108-15 cells with an IC50 value of 6.6 mu M. However, alpha-eudesmol had little inhibito ry effect on L-type Ca2+ channel currents. Thus, the present data indicated that alpha-eudesmol is a potent nonpeptidergic compound which blocks the p resynaptic omega-Aga-IVA-sensitive Ca2+ channel with relative selectivity. (C) 1999 Elsevier Science B.V. All rights reserved.