title: Acetylcholine-induced AMP-activated protein kinase activation attenuates vasoconstriction through an LKB1-dependent mechanism in rat aorta.
abstract: Numerous studies of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries have been reported since the original description by Furchgott and Zawadzki (1980). ACh also produces endothelium-independent relaxation. However, it is still unknown whether ACh-induced AMP-activated protein kinase (AMPK) activation can attenuate vasoconstriction in endothelium-denuded rat aorta. Here, we investigated whether ACh may exert a regulatory effect for vascular tone via AMPK activation and its underlying mechanism in vascular smooth muscle cells (VSMCs). Western blotting showed that ACh dose- and time-dependently increased LKB1 and AMPK phosphorylation in VSMCs. The ACh-induced activation of AMPK required muscarinic receptors in VSMCs. LKB1 and AMPK activation by ACh inhibited myosin light-chain kinase (MLCK) and phosphorylated myosin light chain (p-MLC) expression in VSMCs. In addition, a tension study showed the inhibitory effect of ACh-induced AMPK activation on phenylephrine-mediated contraction in endothelium-denuded rat aorta. These data suggest that the ACh-induced activation of AMPK may attenuate vasoconstriction via LKB1-AMPK-dependent mechanism in endothelium-denuded rat aorta.
authors.affiliation: Department of Pharmacology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, 705-717, Korea.
authors.forename: Kyung Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Hyoung Chul
authors.initials: HC
authors.lastname: Choi
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D018994:Myosin Light Chains / Q000187:drug effects / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018994:Myosin Light Chains; D014665:Vasodilator Agents; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D009219:Myosin-Light-Chain Kinase; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000109:Acetylcholine
keywords: AMPK; Acetylcholine (ACh); LKB1; Vascular smooth muscle cell (VSMC)