Vascular activity of a natural diterpene isolated from Croton zambesicus and of a structurally similar synthetic trachylobane.
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.
Martinsen
Anneloes
A
Université Catholique de Louvain, Laboratoire de Physiologie Cellulaire, Avenue Hippocrate 55, FYCL 5540, B 1200 Brussels, Belgium.
Baccelli
Chiara
C
Navarro
Ismael
I
Abad
Antonio
A
Quetin-Leclercq
Joëlle
J
Morel
Nicole
N
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D029802:Croton; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004224:Diterpenes; D010936:Plant Extracts