Mechanisms of vasorelaxation induced by oleoylethanolamide in the rat small mesenteric artery

被引:22
作者
AlSuleimani, Yousuf M. [1 ,2 ]
Hiley, C. Robin [1 ]
机构
[1] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England
[2] Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Pharmacol & Clin Pharm, Alkoudh 123, Oman
关键词
Oleoylethanolamide; Vasorelaxation; Cannabinoid receptors; Nitric oxide; Ca2+-activated K+ channels; Phospholipase C; ANANDAMIDE-INDUCED VASORELAXATION; ACTIVATED POTASSIUM CHANNELS; PHOSPHOLIPASE-C-EPSILON; NITRIC-OXIDE; CANNABINOID RECEPTOR; ENDOTHELIAL-CELLS; VASCULAR ENDOTHELIUM; CORONARY-ARTERIES; SELECTIVE LIGANDS; CA2+ SENSITIVITY;
D O I
10.1016/j.ejphar.2013.01.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The actions of the anandamide-like mono-unsaturated fatty acid oleoylethanolamide (OEA) were first linked to satiety and control of food intake and recently reported to relax resistance vessels. This study characterizes its vasorelaxant mechanisms. Vasorelaxation to OEA were assessed in third order branches of rat superior mesenteric artery using a wire myograph. The roles of the endothelium, KCa channels, perivascular sensory nerves, NO, cannabinoid receptors, and the phospholipase C (PLC)/inositol trisphosphate (InsP3) and RhoA/ROCK signalling pathways, were assessed. OEA caused concentration- and endothelium-dependent vasorelaxation (pEC50=6.7 +/- 0.1, Rmax=93.1 +/- 2.5%). L-NAME greatly reduced the response (residual relaxation of only 24.6 +/- 12.8%). Capsaicin and pertussis toxin significantly reduced the vasorelaxation. Precontraction with KCl abolished the response. TRAM-34 had no effect, but both iberiotoxin and apamin+charybdotoxin markedly shifted the OEA concentration-response curve to the right (similar to 5-fold). O-1918 but not rimonabant attenuated the vasorelaxation. Both the CBI receptor antagonist, AM251 and the CB2 receptor antagonist, AM630, given alone or in combination, reduced the response to IDEA. Inhibition of PLC by U73122, ROCK by Y-27632 and antagonism of inositol trisphosphate (InsP3) receptors by 2-APB abolished OEA vasorelaxation. OEA vasorelaxation involves an endothelial site of action but not the known cannabinoid receptors. It involves Ca2+ released from InsP3-sensitive endothelial stores by mechanisms involving RhoA kinase and phospholipase C. It is likely that the released Ca2+ causes NO generation and opening of mainly large-conductance K-Ca channels. This study demonstrates a possible novel endothelial target that might be important in the control of regional blood flow induced by this lipid molecule. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.
引用
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页码:1 / 11
页数:11
相关论文
共 70 条
  • [1] Endothelium-derived nitric oxide and vascular physiology and pathology
    Arnal, JF
    Dinh-Xuan, AT
    Pueyo, M
    Darblade, B
    Rami, J
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 55 (8-9) : 1078 - 1087
  • [2] Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine
    Artmann, Andreas
    Petersen, Gitte
    Hellgren, Lars I.
    Boberg, Julie
    Skonberg, Christian
    Nellemann, Christine
    Hansen, Steen Honore
    Hansen, Harald S.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2008, 1781 (04): : 200 - 212
  • [3] G protein-coupled endothelial receptor for atypical cannabinoid ligands modulates a Ca2+-dependent K+ current
    Begg, M
    Mo, FM
    Offertáler, L
    Bátkai, S
    Pacher, P
    Razdan, RK
    Lovinger, DM
    Kunos, G
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (46) : 46188 - 46194
  • [4] An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity
    Ben-Shabat, S
    Fride, E
    Sheskin, T
    Tamiri, T
    Rhee, MH
    Vogel, Z
    Bisogno, T
    De Petrocellis, L
    Di Marzo, V
    Mechoulam, R
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1998, 353 (01) : 23 - 31
  • [5] Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes
    Bisogno, T
    Maurelli, S
    Melck, D
    DePetrocellis, L
    DiMarzo, V
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (06) : 3315 - 3323
  • [6] BLEASDALE JE, 1989, ADV PROSTAG THROMB L, V19, P590
  • [7] BLEASDALE JE, 1990, J PHARMACOL EXP THER, V255, P756
  • [8] Leukemia-associated Rho guanine nucleotide exchange factor promotes Gαq-coupled activation of RhoA
    Booden, MA
    Siderovski, DP
    Der, CJ
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (12) : 4053 - 4061
  • [9] Role of acylethanolamides in the gastrointestinal tract with special reference to food intake and energy balance
    Borrelli, Francesca
    Izzo, Angelo A.
    [J]. BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 23 (01) : 33 - 49
  • [10] Modulation of Ca2+-activated K+ channel in renal artery endothelium in situ by nitric oxide and reactive oxygen species
    Brakemeier, S
    Eichler, I
    Knorr, A
    Fassheber, T
    Köhler, R
    Hoyer, J
    [J]. KIDNEY INTERNATIONAL, 2003, 64 (01) : 199 - 207