title: The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1: Expression and action in brain.
abstract: We have proposed that lactate is a "volume transmitter" in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes the cerebral neocortex and the hippocampus, where it can be stimulated by physiological concentrations of lactate and by the HCAR1 agonist 3,5-dihydroxybenzoate to reduce cAMP levels. Cerebral HCAR1 is concentrated on the postsynaptic membranes of excitatory synapses and also is enriched at the blood-brain barrier. In synaptic spines and in adipocytes, HCAR1 immunoreactivity is also located on subplasmalemmal vesicular organelles, suggesting trafficking to and from the plasma membrane. Through activation of HCAR1, lactate can act as a volume transmitter that links neuronal activity, cerebral blood flow, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress, and schizophrenia and in the deposition of phosphorylated tau protein in Alzheimer's disease. HCAR1 could serve to ameliorate these conditions and might also act through downstream mechanisms other than cAMP. Lactate exits cells through monocarboxylate transporters in an equilibrating manner and through astrocyte anion channels activated by depolarization. In addition to locally produced lactate, lactate produced by exercising muscle as well as exogenous HCAR1 agonists, e.g., from fruits and berries, might activate the receptor on cerebral blood vessels and brain cells.
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.|The Brain and Muscle Energy Group, Department of Oral Biology, University of Oslo, Oslo, Norway.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Morland
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Knut Husø
authors.initials: KH
authors.lastname: Lauritzen
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Maja
authors.initials: M
authors.lastname: Puchades
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Holm-Hansen
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Krister
authors.initials: K
authors.lastname: Andersson
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Institute for Surgical Research, Oslo University Hospital, Oslo, Norway.|Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Håvard
authors.initials: H
authors.lastname: Attramadal
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Storm-Mathisen
authors.affiliation: The Brain and Muscle Energy Group, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.|Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.|Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Linda Hildegard
authors.initials: LH
authors.lastname: Bergersen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C533610:HCAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D019344:Lactic Acid
keywords: cAMP; hippocampus; lactate; volume transmitter