Occurrence and Biosynthesis of Endogenous Cannabinoid Precursor,N-Arachidonoyl Phosphatidylethanolamine, in Rat Brain
Occurrence and Biosynthesis of Endogenous Cannabinoid Precursor,N-Arachidonoyl Phosphatidylethanolamine, in Rat Brain
复制标题
内源性大麻素前体 N-花生四烯酰磷脂酰乙醇胺在大鼠脑中的存在和生物合成
作者：
H. Cadas;E. di Tomaso;D. Piomelli
N-花生四烯基乙醇胺是一种内源性大麻素类物质，可能是通过钙离子刺激磷脂酰乙醇胺(PE)衍生物N-花生四烯基乙醇胺的水解而产生的。然而，成人脑组织中N-花生四烯醇酰PE的存在及其生物合成的酶途径仍未确定。用气相色谱/质谱法测定，大鼠脑组织中既含有花生胺(11±7 pmol/g湿组织)，又含有N-花生四烯醇酰PE(22±16 pmol/g)。我们描述了脑中AN-酰基转移酶的活性，该酶通过将一个花生四烯酸基从磷脂的sn-1碳转移到PE的氨基上来催化N-花生四烯酸PE的生物合成。我们还发现，脑中存在SN-1花生四烯基甲酰磷脂，它们占∼总磷脂的0.5%。N-酰基转移酶的活性依赖于钙离子，并在脑和睾丸中丰富。在大脑内，N-酰基转移酶的活性在脑干中最高，在皮质、纹状体、海马体、延髓和小脑中居中，在丘脑、下丘脑和嗅球中最低。在原代培养的皮质神经元中抑制N-酰基转移酶活性的药理作用可阻止钙离子刺激的N-花生四烯酸乙酯的生物合成。因此，我们的结果表明，大鼠脑组织中含有合成花生胺前体N-花生四烯酸乙酯所必需的酶活性和脂质底物的补充物。他们还提出，N-花生四烯酰基PE的生物合成和花生胺的形成是紧密耦合的过程，可能同时受到神经活动过程中细胞内钙离子升高的刺激。
It has been suggested that anandamide (N-arachidonoylethanolamine), an endogenous cannabinoid substance, may be produced through Ca2+-stimulated hydrolysis of the phosphatidylethanolamine (PE) derivative N-arachidonoyl PE. The presence of N-arachidonoyl PE in adult brain tissue and the enzyme pathways that underlie its biosynthesis are, however, still undetermined. We report here that rat brain tissue contains both anandamide (11 ± 7 pmol/gm wet tissue) andN-arachidonoyl PE (22 ± 16 pmol/gm), as assessed by gas chromatography/mass spectrometry. We describe aN-acyltransferase activity in brain that catalyzes the biosynthesis of N-arachidonoyl PE by transferring an arachidonate group from the sn-1 carbon of phospholipids to the amino group of PE. We also show that sn-1 arachidonoyl phospholipids are present in brain, where they constitute ∼0.5% of total phospholipids. N-acyltransferase activity is Ca2+ dependent and is enriched in brain and testis. Within the brain, N-acyltransferase activity is highest in brainstem; intermediate in cortex, striatum, hippocampus, medulla, and cerebellum; and lowest in thalamus, hypothalamus, and olfactory bulb. Pharmacological inhibition ofN-acyltransferase activity in primary cultures of cortical neurons prevents Ca2+-stimulatedN-arachidonoyl PE biosynthesis. Our results demonstrate, therefore, that rat brain tissue contains the complement of enzymatic activity and lipid substrates necessary for the biosynthesis of the anandamide precursor N-arachidonoyl PE. They also suggest that biosynthesis of N-arachidonoyl PE and formation of anandamide are tightly coupled processes, which may concomitantly be stimulated by elevations in intracellular Ca2+ occurring during neural activity.
登录
查看更多内容
DOI：
--
发表时间：
1995-05
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
S. Deadwyler;R. Hampson;J. Mu;A. Whyte;S. Childers
通讯作者：
S. Deadwyler;R. Hampson;J. Mu;A. Whyte;S. Childers
大麻素调节培养的海马神经元中的钾电流。
DOI：
--
发表时间：
1993
期刊：
Receptors & channels
影响因子：
--
作者：
Deadwyler,SA;Hampson,RE;Bennett,BA;Edwards,TA;Mu,J;Pacheco,MA;Ward,SJ;Childers,SR
通讯作者：
Childers,SR
Anandamide 是一种内源性大麻素，作为 N18 神经母细胞瘤细胞的部分激动剂抑制钙电流。
影响因子：
3.6
作者：
Mackie,K;Devane,WA;Hille,B
通讯作者：
Hille,B
通过转酰基酶活性对狗心脏乙醇胺磷脂进行 N-酰化。
DOI：
10.1016/0005-2760(83)90187-x
发表时间：
1983
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Reddy,PV;Natarajan,V;Schmid,PC;Schmid,HH
通讯作者：
Schmid,HH
DOI：
10.1073/pnas.90.16.7656
发表时间：
1993-08-15
影响因子：
11.1
作者：
FELDER, CC;BRILEY, EM;DEVANE, WA
通讯作者：
DEVANE, WA