Lauritzen Knut H, Morland Cecilie, Puchades Maja, Holm-Hansen Signe, Hagelin Else Marie, Lauritzen Fredrik, Attramadal Håvard, Storm-Mathisen Jon, Gjedde Albert, Bergersen Linda H
The Brain and Muscle Energy Group, Department of Neuroscience and Pharmacology, Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
The Brain and Muscle Energy Group, Glio- and Neurotransmitter Group, Synaptic Neurochemistry Lab, Department of Anatomy and Centre for Molecular Biology and Neuroscience/SERTA Healthy Brain Aging, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Cereb Cortex. 2014 Oct;24(10):2784-95. doi: 10.1093/cercor/bht136. Epub 2013 May 21.
The G-protein-coupled lactate receptor, GPR81 (HCA1), is known to promote lipid storage in adipocytes by downregulating cAMP levels. Here, we show that GPR81 is also present in the mammalian brain, including regions of the cerebral neocortex and hippocampus, where it can be activated by physiological concentrations of lactate and by the specific GPR81 agonist 3,5-dihydroxybenzoate to reduce cAMP. Cerebral GPR81 is concentrated on the synaptic membranes of excitatory synapses, with a postsynaptic predominance. GPR81 is also enriched at the blood-brain-barrier: the GPR81 densities at endothelial cell membranes are about twice the GPR81 density at membranes of perivascular astrocytic processes, but about one-seventh of that on synaptic membranes. There is only a slight signal in perisynaptic processes of astrocytes. In synaptic spines, as well as in adipocytes, GPR81 immunoreactivity is located on subplasmalemmal vesicular organelles, suggesting trafficking of the protein to and from the plasma membrane. The results indicate roles of lactate in brain signaling, including a neuronal glucose and glycogen saving response to the supply of lactate. We propose that lactate, through activation of GPR81 receptors, can act as a volume transmitter that links neuronal activity, cerebral energy metabolism and energy substrate availability.
G蛋白偶联乳酸受体GPR81（HCA1）通过下调cAMP水平促进脂肪细胞中的脂质储存。在此，我们发现GPR81也存在于哺乳动物大脑中，包括大脑新皮质和海马体区域，在这些区域它可被生理浓度的乳酸以及特异性GPR81激动剂3,5 - 二羟基苯甲酸激活，从而降低cAMP水平。脑内GPR81集中在兴奋性突触的突触膜上，以突触后为主。GPR81在血脑屏障处也有富集：内皮细胞膜上的GPR81密度约为血管周围星形胶质细胞突起膜上GPR81密度的两倍，但约为突触膜上密度的七分之一。星形胶质细胞的突触周围突起中只有微弱信号。在突触棘以及脂肪细胞中，GPR81免疫反应性位于质膜下囊泡细胞器上，表明该蛋白在质膜内外的运输。这些结果表明乳酸在脑信号传导中的作用，包括对乳酸供应的神经元葡萄糖和糖原节省反应。我们提出，乳酸通过激活GPR81受体，可作为一种容积传递体，连接神经元活动、脑能量代谢和能量底物可用性。
