Being able to distinguish the pathways involved in regulating oxalate transfer is necessary to understand: (1) the contribution of the intestine to systemic oxalate homeostasis, (2) the pathophysiology of oxalate-associated disorders, particularly those linked to GI dysfunction, (3) how the oxalate-degrading gut bacterium interacts with the epithelium to modify oxalate transfer and (4) to assist identifying potential targets and pathways that might serve the development of future therapeutics. Protein Kinase C (PKC) has received a great deal of attention recently, having been identified as a key negative regulator of PAT1-mediated oxalate transport, across species (human or Quinagolide hydrochloride mouse PAT1) and in different experimental systems (oocytes, T84 cells, Caco-2 cells, native epithelium) [97, 104, 105]. across the intestine. We also discuss some of the numerous physiological stimuli and signaling pathways which have been suggested to participate in the adaptation and regulation of intestinal KMT6 oxalate transport. Finally, we offer an update on research into [7C9]. As a valuable extra-renal pathway for eliminating oxalate, knowing how the intestine transports this anion is essential. Illuminating the mechanisms responsible for absorption and secretion has garnered considerable interest, not only for understanding oxalate homeostasis but also for the development of future therapeutic approaches to tackling hyperoxaluria and kidney stone disease. Realizing this potential demands a fundamental understanding of oxalate transport and how it is regulated. Over the past 35 years, four major discoveries have come to shape our present knowledge. The first came in 1980 with the statement of an active component to intestinal oxalate transport [10]. The second was subsequent studies revealing the amazing adaptive capacity of the intestine, where it could be induced to either actively absorb or secrete oxalate on a net basis in response to numerous local and systemic stimuli [5, 11C13]. The third came with the isolation and identification of [14, 15], but more specifically, its unique ability to induce active oxalate secretion by the intestine [7C9]. The final key development has been identification of the SLC26 (SoLute Carrier) gene family of anion exchangers and the pivotal functions some of these individual transporters Quinagolide hydrochloride play in oxalate transport by the intestine [16C19]. For more expansive background information on these and other facets of intestinal oxalate transport readers are directed to prior authoritative reviews [20, 21]. The intention of this present review is usually to provide an update of recent developments and advances that have taken place in the field over the past 10 years. The pathways and mechanisms for oxalate transport across the intestine Overview The transport of oxalate by the intestine can be categorized based on the pathway it takes across the epithelium and the underlying mechanism involved. Broadly speaking, these are paracellular and passive and transcellular and active. The former entails oxalate moving between the epithelial cells in response to the prevailing transepithelial electrical and concentration gradients Quinagolide hydrochloride acting upon the oxalate anion, and also the properties of the tight junctions. For the transcellular pathway, oxalate techniques through the cells and this must be facilitated by membrane-bound transport proteins located within the apical and basolateral membranes (Fig. 1). The absorption and secretion of oxalate occur simultaneously across the intestinal epithelium. The absorptive oxalate flux from the lumen (mucosal) to the blood (serosal), denoted oocyte expression system has also been commonly used in this regard. Furthermore, the experimental conditions and how oxalate transport has been measured in all of these different systems vary too, from transepithelial fluxes and calculations of permeability, to cellular uptakes and efflux. Such diversity has produced a wealth of valuable information contributing enormously to advancing this area, but at the same time it has generated complexity and lack of consensus. As such, the data presented in the published literature necessitates careful interpretation. We recommend the reader bear this in mind when drawing their own conclusions from the following discussions. Intestinal oxalate absorption The favorable transepithelial electrochemical gradient that exists in vivo (i.e., typical lumen-negative potential difference and low micro-molar blood oxalate) makes the paracellular route a large contributor to absorption in this settingdepending on the amount of soluble, unbound oxalate available within the Quinagolide hydrochloride lumen and the corresponding permeability of.