11月29日,,據(jù)國(guó)外媒體報(bào)道,,美國(guó)研究人員宣布,他們研發(fā)了一種新方法,,可以促進(jìn)大腦中自然產(chǎn)生的大麻發(fā)揮更大的止痛作用,,這為研發(fā)新的止痛藥物鋪平了道路。該研究報(bào)告發(fā)表在最新一期的頂級(jí)科學(xué)雜志《自然·神經(jīng)科學(xué)》上,。
美國(guó)加州大學(xué)歐文分校的藥理學(xué)教授丹尼爾·皮歐梅利(Daniele Piomelli)領(lǐng)導(dǎo)的一個(gè)科學(xué)家小組能使大腦中自然產(chǎn)生的類似大麻的化合物發(fā)揮更大的作用,。這種化合物分子被稱為anandamide,從本質(zhì)上講,,它是一種神經(jīng)傳遞素,是人類大 腦中的大麻素系統(tǒng)的一部分,,它的作用與大麻植物中最主要的成分—四氫大麻醇(tetrahydrocannabinol,THC)極為類似,。有趣的是,這個(gè)特殊的分子可以起到緩解疼痛感,、控制焦慮,、減輕抑郁、控制食物攝入量的作用,,因此,,研制新一代止痛藥的關(guān)鍵在于使anandamide發(fā)揮更大的止痛作用,從而對(duì)許多疾病提供最自然的有效治療方法,。
該研究小組經(jīng)過(guò)研究發(fā)現(xiàn),,抑制FLAT蛋白質(zhì)的產(chǎn)生可促進(jìn)anandamide的效用水平。丹尼爾解釋說(shuō),,F(xiàn)LAT是將內(nèi)源性大麻素(endocannabinoid)運(yùn)輸?shù)交衔锎x處的分子,。科學(xué)家們希望,,在不久的將來(lái),,他們能夠研制出新的一代的止痛藥。這些藥物的特點(diǎn)是對(duì)人體沒(méi)有副作用,,不會(huì)使人上癮,,對(duì)中樞神經(jīng)系統(tǒng)不會(huì)造成損害。丹尼爾說(shuō):“這些發(fā)現(xiàn)使科學(xué)家有望研發(fā)具有大麻鎮(zhèn)痛特性的安全的新型止痛藥物,。”
意大利帕爾馬大學(xué)(University of Parma)和博洛尼亞大學(xué)(University of Bologna),,以及意大利技術(shù)研究所的科學(xué)家們也參與了這項(xiàng)研究。此項(xiàng)研究成果表明,科學(xué)利用大麻,,從大麻中提取有用的成分,,可以對(duì)人體產(chǎn)生積極而健康的影響。(生物谷 Bioon.com)
doi:10.1038/nn.2986
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PMID:
A catalytically silent FAAH-1 variant drives anandamide transport in neurons
Jin Fu,, Giovanni Bottegoni,, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau, Tiziano Bandiera, Angelo Reggiani, Marco Mor, Andrea Cavalli, & Daniele Piomelli,
The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, that remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, blocked these effects. We also identified a competitive antagonist of the interaction of anandamide with FLAT, the phthalazine derivative ARN272, that prevented anandamide internalization in vitro, interrupted anandamide deactivation in vivo and exerted profound analgesic effects in rodent models of nociceptive and inflammatory pain, which were mediated by CB1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs.