Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as an L-type calcium channel blocker.
1. The objective of the present study was to investigate the mechanism of the relaxant activity of marrubenol, a diterpenoid extracted from Marrubium vulgare. In rat aorta, marrubenol was a more potent inhibitor of the contraction evoked by 100 mM KCl (IC50: 11.8+/-0.3 microM, maximum relaxation: 93+/-0.6%) than of the contraction evoked by noradrenaline (maximum relaxation: 30+/-1.5%). 2. In fura-2-loaded aorta, marrubenol simultaneously inhibited the Ca2+ signal and the contraction evoked by 100 mM KCl, and decreased the quenching rate of fura-2 fluorescence by Mn2+. 3. Patch-clamp data obtained in aortic smooth muscle cells (A7r5) indicated that marrubenol inhibited Ba2+ inward current in a voltage-dependent manner (KD: 8+/-2 and 40+/-6 microM at holding potentials of -50 and -100 mV, respectively). 4. These results showed that marrubenol inhibits smooth muscle contraction by blocking L-type calcium channels.
Laboratoire de Pharmacologie, Université catholique de Louvain, UCL 5410, Avenue Hippocrate, 54, Bruxelles B-1200, Belgium.
Sanae
S
El-Bardai
Maurice
M
Wibo
Marie-Christine
MC
Hamaide
Badiaa
B
Lyoussi
Joelle
J
Quetin-Leclercq
Nicole
N
Morel
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001464:Barium / Q000037:antagonists & inhibitors; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016257:Fura-2; D008297:Male; D027522:Marrubium / Q000737:chemistry*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010936:Plant Extracts; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004224:Diterpenes; D005456:Fluorescent Dyes; D010936:Plant Extracts; D001464:Barium; D011189:Potassium Chloride; D002118:Calcium; D016257:Fura-2