Laboratorio de Enzimología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
PLoS One. 2012;7(4):e34562. doi: 10.1371/journal.pone.0034562. Epub 2012 Apr 11.
Hydrogen sulfide (H(2)S) is mainly known for its toxicity but has recently been shown to be produced endogenously in mammalian tissues and to be associated with physiological regulatory functions. To better understand the role of biomembranes in modulating its biological distribution and effects; we measured the partition coefficient of H(2)S in models of biological membranes. The partition coefficients were found to be 2.1±0.2, 1.9±0.5 and 2.0±0.6 in n-octanol, hexane and dilauroylphosphatidylcholine liposome membranes relative to water, respectively (25°C). This two-fold higher concentration of H(2)S in the membrane translates into a rapid membrane permeability, P(m) = 3 cm s(-1). We used a mathematical model in three dimensions to gain insight into the diffusion of total sulfide in tissues. This model shows that the sphere of action of sulfide produced by a single cell expands to involve more than 200 neighboring cells, and that the resistance imposed by lipid membranes has a significant effect on the diffusional spread of sulfide at pH 7.4, increasing local concentrations. These results support the role of hydrogen sulfide as a paracrine signaling molecule and reveal advantageous pharmacokinetic properties for its therapeutic applications.
硫化氢 (H₂S) 主要因其毒性而为人所知，但最近已被证明在哺乳动物组织中内源性产生，并与生理调节功能相关。为了更好地了解生物膜在调节其生物分布和作用中的作用；我们测量了 H₂S 在生物膜模型中的分配系数。在正辛醇、己烷和二棕榈酰磷脂酰胆碱脂质体膜相对于水的分配系数分别为 2.1±0.2、1.9±0.5 和 2.0±0.6（25°C）。这意味着 H₂S 在膜中的浓度是水中的两倍，这使得 H₂S 具有快速的膜通透性，P(m)=3 cm s⁻¹。我们使用三维数学模型深入了解组织中总硫的扩散。该模型表明，单个细胞产生的硫的作用范围扩大到涉及 200 多个相邻细胞，并且脂质膜的阻力对 pH 7.4 时硫的扩散分布有显著影响，增加了局部浓度。这些结果支持硫化氢作为旁分泌信号分子的作用，并揭示了其治疗应用的有利药代动力学特性。
