1. Vascul Pharmacol. 2010 Jan-Feb;52(1-2):63-9. Epub 2009 Nov 29.

Vascular activity of a natural diterpene isolated from Croton zambesicus and of a
structurally similar synthetic trachylobane.

Martinsen A, Baccelli C, Navarro I, Abad A, Quetin-Leclercq J, Morel N.

Université Catholique de Louvain, Laboratoire de Physiologie Cellulaire, Avenue
Hippocrate 55, FYCL 5540, B 1200 Brussels, Belgium.

The aim of this study was to determine the vasorelaxant activity of a natural
diterpene extracted from Croton zambesicus, ent-18-hydroxy-trachyloban-3-one
(DT6), and a synthetic diterpene of similar structure,
ent-trachyloban-14,15-dione (DT10) in rat aorta. DT6 and DT10 inhibited aorta
contraction in a concentration-dependent manner. Both were more potent inhibitors
of KCl-evoked contraction than noradrenaline-evoked contraction. Nitric oxide
(NO) synthase inhibition did not significantly affect DT6 effect whereas it
significantly decreased DT10 inhibitory potency. In fura-2 loaded aorta rings,
DT10 simultaneously inhibited KCl-evoked contraction and cytosolic calcium
increase in a concentration-dependent manner. Furthermore, DT10 significantly
inhibited calcium channel current recorded by the patch-clamp technique in human 
neuroblastoma cells SH-SY5Y. However, despite potentiation of
8-bromo-cGMP-response, DT6 and DT10 as verapamil depressed acetylcholine-evoked
relaxation, DT6 being the most potent, while only DT6 and DT10 depressed
SNAP-evoked relaxation. In conclusion, these data suggest that vasorelaxant
activity of diterpenes (DT) is associated with the blockade of L-type
voltage-operated calcium channels. Inhibition of NO-dependent relaxation by DT
could be related to a decrease in NO availability. 2009 Elsevier Inc. All rights 
reserved.

PMID: 19951744 [PubMed - in process]