Marrubenol interacts with the phenylalkylamine binding site of the L-type calcium channel.
Marrubenol inhibits contraction of rat arteries by blocking L-type calcium (Ca(2+)) channels in smooth muscle cells, but its interaction with binding sites for calcium antagonists had never been investigated. Competition binding studies indicated that marrubenol was a weak inhibitor of 1,4-dihydropyridine binding in membranes isolated from rat intestinal smooth muscle but completely displaced specifically bound (-)-[(3)H]desmethoxyverapamil ([(3)H]D888) with an apparent K(i) value of 16 microM (95% confidence interval: 6.5-39.5 microM). As marrubenol inhibited the contraction evoked by KCl depolarization of intestinal smooth muscle half-maximally at a concentration of approximately 12 microM, interaction with the phenylalkylamine binding site seems to account for the inhibition of L-type Ca(2+) channels by marrubenol.
El Bardai
Sanae
S
Laboratoire de Pharmacologie, Université Catholique de Louvain, UCL 5410, Avenue Hippocrate, 54, B-1200 Brussels, Belgium.
Hamaide
Marie-Christine
MC
Lyoussi
Badiaa
B
Quetin-Leclercq
Joëlle
J
Morel
Nicole
N
Wibo
Maurice
M
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D017275:Isradipine / Q000378:metabolism; D008297:Male; D008566:Membranes; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D004224:Diterpenes; D005663:Furans; D014665:Vasodilator Agents; C473344:marrubenol; D011189:Potassium Chloride; C038806:1,4-dihydropyridine; C043184:4-desmethoxyverapamil; D014700:Verapamil; D017275:Isradipine