Planta Med 2007; 73(14): 1441-1446
DOI: 10.1055/s-2007-990246
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Large Conductance Ca2+-Activated K+ (BKCa) Channels are Involved in the Vascular Relaxations Elicited by Piceatannol Isolated from Rheum undulatum rhizome

Kwang-Seok Oh1 , Shi Yong Ryu1 , Young Sup Kim1 , Byung Ho Lee1
  • 1Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
Further Information

Publication History

Received: July 27, 2007 Revised: September 19, 2007

Accepted: September 21, 2007

Publication Date:
24 October 2007 (online)

Abstract

We previously reported that piceatannol isolated from the rhizome extract of Rheum undulatum has a potent vasorelaxant activity. In the present study, the mechanisms underlying the direct vascular relaxant effect of piceatannol were investigated in isolated rat aorta. Piceatannol induced a concentration-dependent relaxation in aortic preparations precontracted with phenylephrine (EC50 : 2.4 ± 0.4 μM), which was completely inhibited by endothelial removal, N ω-nitro-L-arginine (nitric oxide synthase inhibitor), methylene blue and 1H-[1] [2] [4]oxadiazolo [4,3-a]quinoxalin-1-one (guanylyl cyclase inhibitor). The piceatannol-induced relaxation was also blocked by raising the extracellular K+ (45 mM), 4-aminopyridine (voltage-sensitive K+ channel blocker) and tetraethylammonium [the non-selective Ca2+-activated K+ (KCa) channel blocker] but not by indomethacin (cyclooxygenase inhibitor), atropine (muscarinic receptor antagonist), propranolol (β-adrenoceptor antagonist), verapamil and nifedipine (L-type voltage-gated Ca2+ channel blocker), barium chloride (inward rectifier K+ channel inhibitor) and glibenclamide (ATP-sensitive K+ channel blocker). In further studies investigating the role of Ca2+-activated K+ (KCa) channels, piceatannol-induced relaxant responses were decreased by charybdotoxin [large (BKCa)- and intermediate (IKCa)-conductance KCa channel blocker], iberiotoxin (selective BKCa channels blocker), but not by apamin [small-conductance KCa (SKCa) channel blocker], TRAM-34 [intermediate-conductance KCa (IKCa) channel blocker]. The present results demonstrate that piceatannol-induced vascular relaxation in rat aorta may be mediated by an endothelium-dependent nitric oxide signaling pathway, at least partially, through the activation of BKCa.

Abbreviations

BKCa channel: large conductance KCa channel

IKCa channel: intermediate conductance KCa channel

KATP channel: ATP-sensitive K+ channel

KCa channel: Ca2+-activated K+ channel

KIR channel: inward rectifier K+ channel

Kv channel: voltage-dependent K+ channel

L-NNA: N ω-nitro-L-arginine

MB: methylene blue

ODQ: 1H-[1] [2] [4] oxadiazolo[4,3-a]quinoxalin-1-one

SKCa channel: small conductance KCa channel

TEA: tetraethylammonium

TRAM 34: 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole

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Byung Ho Lee, PhD

Drug Discovery Division

Korea Research Institute of Chemical Technology

100 Jang-dong

Yuseong

Daejeon 305-343

Republic of Korea

Phone: +82-42-860-7415

Fax: +82-42-861-4246

Email: bhlee@krict.re.kr