Roberts Claire, Winter Panida, Shilliam Claire S, Hughes Zoe A, Langmead Christopher, Maycox Peter R, Dawson Lee A
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK.
Neurochem Res. 2005 Mar;30(3):371-7. doi: 10.1007/s11064-005-2611-6.
LPA1 is a Gi-coupled seven transmembrane receptor with high affinity for the ligand lysophosphatidic acid. We have investigated the effect of targeted deletion at the lpa1 locus on evoked release of amino acids from hippocampal slices, using in vitro superfusion techniques, and evoked 5-HT efflux from the dorsal raphe nucleus, using in vitro fast cyclic voltammetry. Superfusion of hippocampal slices revealed that basal levels of tyrosine, aspartate and glutamate release were significantly increased while K+ -evoked release of glutamate and GABA were significantly decreased in lpa1(-/-) mice. Fast cyclic voltammetry measurements in the dorsal raphe nucleus demonstrated significant decreases in electrically evoked 5-HT efflux in lpa1(-/-) mice. In summary, these data demonstrate that the lpa1 mutation produces a number of changes in neurotransmitters that have been associated with a schizophrenic-like pathology.
LPA1是一种与Gi偶联的七跨膜受体，对溶血磷脂酸配体具有高亲和力。我们利用体外灌流技术研究了lpa1基因座靶向缺失对海马切片中氨基酸诱发释放的影响，并利用体外快速循环伏安法研究了其对背侧中缝核中5-羟色胺流出的影响。海马切片灌流显示，lpa1基因敲除小鼠中酪氨酸、天冬氨酸和谷氨酸的基础释放水平显著增加，而钾离子诱发的谷氨酸和γ-氨基丁酸释放显著减少。背侧中缝核的快速循环伏安法测量表明，lpa1基因敲除小鼠中电诱发的5-羟色胺流出显著减少。总之，这些数据表明，lpa1突变在神经递质中产生了许多与精神分裂症样病理相关的变化。
