Fernandez J M, Villalón M, Verdugo P
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
Biophys J. 1991 May;59(5):1022-7. doi: 10.1016/S0006-3495(91)82317-7.
We have investigated the mechanisms responsible for the condensation and decondensation of secretory products that occur in mast cell secretion. We show here that the hydrated matrix of an exocytosed secretory granule can be recondensed to its original volume by exposure to acidic solutions containing histamine at concentrations that mimic those found in vivo. Recondensation by acidic histamine began in the range of 1-10 mM with a dose response curve that was accurately predicted by a Hill type equation with four highly cooperative binding sites and a half maximum concentration of [Hi++] = 3.9 mM. Recondensation by histamine showed a sigmoidal dependency on pH (critical range pH 5.5-6.5) and was fully reversible. These experiments suggest that histamine, possibly by binding to anionic sites in the protein-heparin complex of the granule matrix, triggers a change in the polymeric structures of the granule matrix from an extended coil to a collapsed globular state. This may be a useful model for understanding the condensation of secretory products into dense core granules and their subsequent decondensation upon exocytosis.
我们研究了肥大细胞分泌过程中分泌产物凝聚和去凝聚的机制。我们在此表明，通过暴露于含有组胺的酸性溶液中，胞吐分泌颗粒的水合基质可以重新凝聚至其原始体积，该酸性溶液中组胺的浓度模拟体内发现的浓度。酸性组胺引起的重新凝聚在1-10 mM范围内开始，其剂量反应曲线由具有四个高度协同结合位点且半最大浓度[Hi++] = 3.9 mM的希尔型方程准确预测。组胺引起的重新凝聚对pH呈S形依赖性（临界范围pH 5.5-6.5）且完全可逆。这些实验表明，组胺可能通过与颗粒基质的蛋白质-肝素复合物中的阴离子位点结合，触发颗粒基质的聚合物结构从伸展的线圈状变为塌陷的球状。这可能是一个有助于理解分泌产物凝聚成致密核心颗粒及其随后在胞吐作用时去凝聚的有用模型。
