Characterization of cannabinoid receptors coupled to vasorelaxation by endothelium-derived hyperpolarizing factor

被引:15
作者
Harris, D [1 ]
Kendall, DA [1 ]
Randall, MD [1 ]
机构
[1] Univ Nottingham, Sch Med, Sch Biomed Sci, Queens Med Ctr, Nottingham NG7 2UH, England
关键词
endothelium; endothelium-derived hyperpolarizing factor (EDHF); cannabinoids; LY320135; AM630; SR144528;
D O I
10.1007/PL00005322
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have recently proposed that an endogenous cannabinoid may be an endothelium-derived hyperpolarizing factor (EDHF), and we have now characterized the cannabinoid receptors mediating these responses. EDHF-mediated vasorelaxations to carbachol (ED50=3.26+/-0.57 nmol; the maximum relaxation, R-max=87.0+/-2.5%) were opposed by the selective cannabinoid CB1 antagonist, LY320135: at 2 mu M ED50 for carbachol was 10.4+/-2.6 nmol and R-max was 66.9+/-6.2%, at 10 mu M ED50 was 15.9+/-4.0 nmol and R-max was 34.0+/-4.3%. However, these responses were unaffected by another putative CB1 ligand, AM630 (10 mu M), or a CB2 selective antagonist, SR144528 (100 nM-1 mu M). None of the antagonists influenced vasorelaxation to either the potassium channel activator levcromakalim or sodium nitroprusside. Coupled to our previous observation that the CB1 receptor antagonist SR141716A opposes EDHF-mediated relaxation, the present observations point to the involvement of a cannabinoid receptor, which may be CB1 or CB1-like, in EDHF-mediated vasorelaxation.
引用
收藏
页码:48 / 52
页数:5
相关论文
共 23 条
[1]   Cannabinoid CB1 receptor and endothelium-dependent hyperpolarization in guinea-pig carotid, rat mesenteric and porcine coronary arteries [J].
Chataigneau, T ;
Félétou, M ;
Thollon, C ;
Villeneuve, N ;
Vilaine, JP ;
Duhault, J ;
Vanhoutte, PM .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 123 (05) :968-974
[2]   Production and physiological actions of anandamide in the vasculature of the rat kidney [J].
Deutsch, DG ;
Goligorsky, MS ;
Schmid, PC ;
Krebsbach, RJ ;
Schmid, HHO ;
Das, SK ;
Dey, SK ;
Arreaza, G ;
Thorup, C ;
Stefano, G ;
Moore, LC .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (06) :1538-1546
[3]  
Felder CC, 1998, J PHARMACOL EXP THER, V284, P291
[4]   ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION - A ROLE IN THE CONTROL OF VASCULAR TONE [J].
GARLAND, CJ ;
PLANE, F ;
KEMP, BK ;
COCKS, TM .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1995, 16 (01) :23-30
[5]  
Hewitt N, 1997, BRIT J PHARMACOL, V122, pP122
[6]   AM630 is an inverse agonist at the human cannabinoid CB1 receptor [J].
Landsman, RS ;
Makriyannis, A ;
Deng, HF ;
Consroe, P ;
Roeske, WR ;
Yamamura, HI .
LIFE SCIENCES, 1998, 62 (09) :PL109-PL113
[7]   Evidence for inverse agonism of SR141716A at human recombinant cannabinoid CB1 and CB2 receptors [J].
MacLennan, SJ ;
Reynen, PH ;
Kwan, J ;
Bonhaus, DW .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 124 (04) :619-622
[8]   Modulation of vasorelaxant responses to potassium channel openers by basal nitric oxide in the rat isolated superior mesenteric arterial bed [J].
McCulloch, AI ;
Randall, MD .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (05) :859-866
[9]   Characterization and modulation of EDHF-mediated relaxations in the rat isolated superior mesenteric arterial bed [J].
McCulloch, AI ;
Bottrill, FE ;
Randall, MD ;
Hiley, CR .
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 120 (08) :1431-1438
[10]   Pharmacology of cannabinoid CB1 and CB2 receptors [J].
Pertwee, RG .
PHARMACOLOGY & THERAPEUTICS, 1997, 74 (02) :129-180