Wasserman S I, Barrett K E, Huott P A, Beuerlein G, Kagnoff M F, Dharmsathaphorn K
Department of Medicine, University of California, San Diego 92103.
Am J Physiol. 1988 Jan;254(1 Pt 1):C53-62. doi: 10.1152/ajpcell.1988.254.1.C53.
The mast cell mediator, histamine, induces a rapid and transient increase in chloride secretion across monolayers of the human colonic epithelial cell line, T84. Threshold stimulation occurred at 3 X 10(-6) M histamine and a maximal effect at 10(-4) M. The effect was reproduced by the H1 agonists 2-methylhistamine and 2-pyridylethylamine, but not by the H2 agonists 4-methylhistamine and dimaprit, suggesting the involvement of an H1 receptor. Additionally, histamine's action was inhibited by an H1 antagonist, diphenhydramine, but not by an H2 antagonist, cimetidine. Histamine treatment increased free cytosolic calcium levels, but not those of adenosine 3',5'-cyclic monophosphate (cAMP) or guanosine 3',5'-cyclic monophosphate (cGMP). The mechanism of chloride secretion induced by histamine resembled that of carbachol, in that both 1) were associated with an increase in free cytosolic calcium, 2) had a site of activation at a basolaterally localized K+ channel, and 3) were potentiated by both cAMP- and cGMP-mediated secretagogues. These results suggest that histamine may act as an intestinal secretagogue via direct interactions with epithelial cells.
肥大细胞介质组胺可诱导人结肠上皮细胞系T84单层细胞的氯化物分泌迅速且短暂地增加。阈刺激在组胺浓度为3×10⁻⁶ M时出现，最大效应在10⁻⁴ M时出现。H1激动剂2-甲基组胺和2-吡啶乙胺可重现该效应，但H2激动剂4-甲基组胺和二甲双胍则不能，这表明涉及H1受体。此外，组胺的作用被H1拮抗剂苯海拉明抑制，但未被H2拮抗剂西咪替丁抑制。组胺处理可增加游离胞质钙水平，但不增加3',5'-环磷酸腺苷（cAMP）或3',5'-环磷酸鸟苷（cGMP）的水平。组胺诱导的氯化物分泌机制与卡巴胆碱相似，因为二者：1）均与游离胞质钙增加有关；2）在基底外侧定位的钾通道有一个激活位点；3）均被cAMP和cGMP介导的促分泌剂增强。这些结果表明，组胺可能通过与上皮细胞直接相互作用而作为一种肠道促分泌剂。
