title: 5E- and 5Z-farnesylacetones from Sargassum siliquastrum as novel selective L-type calcium channel blockers.
abstract: A specific blocker of L-type Ca(2+) channels may be useful in decreasing arterial tone by reducing the open-state probability of L-type Ca(2+) channels. The aim of the present study was to evaluate the farnesylacetones, which are major active constituents of Sargassum siliquastrum, regarding their vasodilatation efficacies, selectivities toward L-type Ca(2+) channels, and in vivo antihypertensive activities. The application of 5E-(farnesylacetone 311) or 5Z-farnesylacetone (farnesylacetone 312) induced concentration-dependent vasodilatation effects on the basilar artery that was pre-contracted with depolarization and showed an ignorable potential role of endothelial-derived nitric oxide. We also tested farnesylacetone 311 or 312 to determine their pharmacological profiles for the blockade of native L-type Ca(2+) channels in basilar arterial smooth muscle cells (BASMCs) and ventricular myocytes (VMCs), cloned L- (α1C/β2a/α2δ), N- (α1B/β1b/α2δ), and T-type Ca(2+) channels (α1G, α1H, and α1I). Farnesylacetone 311 or 312 showed greater selectivity toward the L-type Ca(2+) channels among the tested voltage-gated Ca(2+) channels. The ranked order of the potency for farnesylacetone 311 was cloned α1C≒L-type (BASMC)≒L-type (VMCs)>α1B>α1H>α1I>α1G and that for farnesylacetone 312 was cloned α1C≒L-type (BASMCs)≒L-type (VMCs)>α1H>α1G>α1B>α1I. The oral administration of the farnesylacetone 311 (80mg/kg) conferred potent, long-lasting antihypertensive activity in spontaneous hypertensive rats, but it did not alter the heart rate.
authors: Department of Microbiology, College of Medicine, Kwandong University, Gangneung, 210-701, Republic of Korea.
authors: Woon-Seob
authors: WS
authors: Shin
authors: Sangtae
authors: S
authors: Oh
authors: Sung-Wan
authors: SW
authors: An
authors: Gab-Man
authors: GM
authors: Park
authors: Daeho
authors: D
authors: Kwon
authors: Jungyeob
authors: J
authors: Ham
authors: Seokjoon
authors: S
authors: Lee
authors: Byong-Gon
authors: BG
authors: Park
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D001776:Blood Circulation Time; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D044647:Sargassum / Q000737:chemistry*; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D013729:Terpenes; D009569:Nitric Oxide; C014549:farnesylacetone