Succinate receptor C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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Nomenclature as recommended by NC-IUPHAR [1]. The succinate receptor (GPR91, SUCNR1) is activated by the tricarboxylic acid (or Krebs) cycle intermediate succinate and other dicarboxylic acids with less clear physiological relevance such as maleate [6]. Since its pairing with its endogenous ligand in 2004, intense research has focused on the receptor-ligand pair role in various (patho)physiological processes such as regulation of renin production [6,21], ischemia injury [6], fibrosis [11], retinal angiogenesis [17], inflammation [10-11], immune response [16], obesity [8,12,25], diabetes [9,21,24], platelet aggregation [19-20] or cancer [13,27]. The succinate receptor is coupled to Gi/o [3,6] and Gq/11 protein families [6,15,22]. Although the receptor is, upon ligand addition, rapidly desensitized [7,15], and in some cells internalized [6], it seems to recruit arrestins weakly [2]. The cellular activation of the succinate receptor triggers various signalling pathways such as decrease of cAMP levels, [Ca2+]i mobilization and activation of kinases (ERK, c-Jun, Akt, Src, p38, PI3Kβ, etc.) [4]. The receptor is broadly expressed but is notably abundant in immune cells (M2 macrophages [8,22], monocytes [16], immature dendritic cells [16], adipocytes [25], platelets [19-20], etc.) and in the kidney [6].
Receptors
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succinate receptor
C
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Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
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In humans, there is the possibility of two open-reading frames (ORFs) for SUCNR1, one giving a protein of 330 amino acids (AA) and the other one 334-AA. Wittenberger et al. [26] noted that the 330-AA protein was more likely to be expressed given the Kozak sequence surrounding the second ATG. Some databases report SUCNR1 as being 334-AA long.