Schalla Martha A, Oerter Sabrina, Cubukova Alevtina, Metzger Marco, Appelt-Menzel Antje, Stengel Andreas
Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine; Charite-Universitätsmedizin BerlinCorporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 12203 Berlin, Germany.
Department of Gynecology and Obstetrics, HELIOS Kliniken GmbH, 78628 Rottweil, Germany.
Brain Sci. 2023 Jun 22;13(7):980. doi: 10.3390/brainsci13070980.
Phoenixin-14 is a recently discovered peptide regulating appetite. Interestingly, it is expressed in the gastrointestinal tract; however, its supposed receptor, GPR173, is predominantly found in hypothalamic areas. To date, it is unknown how peripherally secreted phoenixin-14 is able to reach its centrally located receptor. To investigate whether phoenixin is able to pass the blood-brain barrier, we used an in vitro mono-culture blood-brain barrier (BBB) model consisting of brain capillary-like endothelial cells derived from human induced-pluripotent stem cells (hiPSC-BCECs). The passage of 1 nMol and 10 nMol of phoenixin-14 via the mono-culture was measured after 30, 60, 90, 120, 150, 180, 210, and 240 min using a commercial ELISA kit. The permeability coefficients (PC) of 1 nMol and 10 nMol phoenixin-14 were 0.021 ± 0.003 and 0.044 ± 0.013 µm/min, respectively. In comparison with the PC of solutes known to cross the BBB in vivo, those of phoenixin-14 in both concentrations are very low. Here, we show that phoenixin-14 alone is not able to cross the BBB, suggesting that the effects of peripherally secreted phoenixin-14 depend on a co-transport mechanism at the BBB in vivo. The mechanisms responsible for phoenixin-14's orexigenic property along the gut-brain axis warrant further research.
胃泌酸调节素-14是一种最近发现的调节食欲的肽。有趣的是，它在胃肠道中表达；然而，其假定的受体GPR173主要存在于下丘脑区域。迄今为止，尚不清楚外周分泌的胃泌酸调节素-14如何能够到达位于中枢的受体。为了研究胃泌酸调节素是否能够穿过血脑屏障，我们使用了一种体外单培养血脑屏障（BBB）模型，该模型由源自人诱导多能干细胞的脑毛细血管样内皮细胞（hiPSC-BCEC）组成。使用商业ELISA试剂盒在30、60、90、120、150、180、210和240分钟后测量1纳摩尔和10纳摩尔胃泌酸调节素-14通过单培养的情况。1纳摩尔和10纳摩尔胃泌酸调节素-14的渗透系数（PC）分别为0.021±0.003和0.044±0.013微米/分钟。与已知在体内穿过血脑屏障的溶质的PC相比，两种浓度的胃泌酸调节素-14的PC都非常低。在这里，我们表明单独的胃泌酸调节素-14不能穿过血脑屏障，这表明外周分泌的胃泌酸调节素-14的作用取决于体内血脑屏障处的共转运机制。胃泌酸调节素-14沿肠-脑轴产生促食欲特性的机制值得进一步研究。
