Zhao C M, Chen D, Lintunen M, Panula P, Håkanson R
Department of Pharmacology, University of Lund, Sölvegatan 10, S-223 62 Lund, Sweden.
Cell Tissue Res. 1999 Jan;295(1):131-40. doi: 10.1007/s004410051219.
The histamine-storing ECL cells in the stomach play a key role in the control of acid secretion. They contain granules, secretory vesicles and microvesicles, and sustained gastrin stimulation results in the additional formation of vacuoles and lipofuscin bodies. The cells are rich in the vesicle monoamine transporter type-2 (VMAT-2), which can be inhibited by reserpine. The present study examines the effect of reserpine on ECL-cell ultrastructure and histamine compartmentalization. Rats received reserpine and/or gastrin. Reserpine was given twice by the intraperitoneal route (25 mg/kg once daily). Gastrin-17 was given by subcutaneous infusion (5 nmol/kg/h), starting at the time of the first reserpine injection and continuing for 4 days when the rats were killed. At this stage, histamine in the oxyntic mucosa was unaffected by reserpine but elevated by gastrin. Immunocytochemical analysis (confocal microscopy) showed ECL-cell histamine in control and gastrin-treated rats to be localized in cytoplasmic organelles (e.g., secretory vesicles). After treatment with reserpine alone or reserpine+gastrin, ECL-cell histamine occurred mainly in the cytosol. Planimetric analysis (electron microscopy) of ECL cells showed reserpine to increase the number, size and volume density of the granules and to reduce the size and volume density of the secretory vesicles. Gastrin reduced the number and volume density of granules and secretory vesicles, increased the number and volume density of microvesicles and caused vacuoles and lipofuscin bodies to appear. Reserpine+gastrin increased the number, volume density and size of the granules. Reserpine prevented the effects of gastrin on secretory vesicles, vacuoles and microvesicles, but did not prevent the development of lipofuscin. Our findings are in line with the views: (1) that preformed cytosolic histamine is taken up by granules/secretory vesicles via VMAT-2, that histamine is instrumental in the transformation of granules into secretory vesicles and in their consequent enlargement and (2) that vacuoles are formed by the fusion of large secretory vesicles.
胃中储存组胺的肠嗜铬样（ECL）细胞在胃酸分泌的控制中起关键作用。它们含有颗粒、分泌囊泡和微囊泡，持续的胃泌素刺激会导致空泡和脂褐素体的额外形成。这些细胞富含2型囊泡单胺转运体（VMAT-2），利血平可抑制该转运体。本研究考察了利血平对ECL细胞超微结构和组胺区室化的影响。给大鼠注射利血平和/或胃泌素。利血平通过腹腔注射给药两次（25mg/kg，每日一次）。胃泌素-17通过皮下输注给药（5nmol/kg/h），从首次注射利血平开始，持续4天，之后处死大鼠。在此阶段，泌酸黏膜中的组胺不受利血平影响，但受胃泌素升高作用影响。免疫细胞化学分析（共聚焦显微镜）显示，对照大鼠和经胃泌素处理的大鼠中，ECL细胞组胺定位于细胞质细胞器（如分泌囊泡）中。单独用利血平或利血平+胃泌素处理后，ECL细胞组胺主要出现在细胞质溶胶中。对ECL细胞的平面测量分析（电子显微镜）显示，利血平可增加颗粒的数量、大小和体积密度，并降低分泌囊泡的大小和体积密度。胃泌素可减少颗粒和分泌囊泡的数量和体积密度，增加微囊泡的数量和体积密度，并导致空泡和脂褐素体出现。利血平+胃泌素可增加颗粒的数量、体积密度和大小。利血平可防止胃泌素对分泌囊泡、空泡和微囊泡的影响，但不能防止脂褐素的形成。我们的研究结果符合以下观点：（1）预先形成的胞质组胺通过VMAT-2被颗粒/分泌囊泡摄取，组胺有助于颗粒转化为分泌囊泡并使其随后增大；（2）空泡由大的分泌囊泡融合形成。
