Majewski Marek, Jaworski Tomasz, Sarosiek Irene, Sostarich Sandra, Roeser Katherine, Edlavitch Stanley A, Kralstein Jeffrey, Wallner Grzegorz, McCallum Richard W, Sarosiek Jerzy
Kansas University Medical Center, Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Center for GI Nerve & Muscle Function, Gastroenterology Research Laboratory, Kansas City, Kansas 66160, USA.
Clin Gastroenterol Hepatol. 2007 Apr;5(4):430-8. doi: 10.1016/j.cgh.2007.01.002.
BACKGROUND & AIMS: Tegaserod, a serotonin 5-hydroxytryptamine (5-HT)4 receptor agonist, is thought to stimulate intestinal secretions. The aim of the current study was to assess the effect of tegaserod vs placebo on salivary and esophageal protective factors in patients with gastroesophageal reflux disease (GERD).
This study was a randomized, double-blind, placebo-controlled, cross-over trial in 38 GERD patients treated with tegaserod 6 mg twice a day vs placebo. Salivary samples were collected basally and during mastication. In addition, in 32 GERD patients, salivary and esophageal secretions also were collected during infusion of NaCl, HCl/pepsin, and NaCl in a consecutive fashion using a specially designed esophageal catheter. Saliva and esophageal perfusates were assessed for the pH, volume, content of buffers, protein, mucin, epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and prostaglandin E (PGE)2 and analyzed statistically.
Salivary flow rates during administration of tegaserod increased over corresponding values during both basal conditions (P < .01) and mastication (P < .001). The rate of secretion of salivary bicarbonate and nonbicarbonate buffers also increased in basal conditions (P < .001 and P < .01, respectively) and during mastication (P < .05 and P = .05). Salivary EGF increased during mastication (P < .05), whereas PGE2 and TGF alpha increased in basal conditions (P < .05 and P < .01). Esophageal perfusate volumes increased during administration of tegaserod in basal conditions (P < .05), whereas esophageal EGF secretion increased after mucosal exposure to HCl/pepsin and subsequent final perfusion with NaCl (P < .05).
Significant stimulatory impact of 5-HT4 agonist on several salivary protective factors as well as esophageal EGF secretion may have esophagoprotective implications in patients with GERD and may help to address new therapies in the future.
替加色罗是一种5-羟色胺（5-HT）4受体激动剂，被认为可刺激肠道分泌。本研究旨在评估替加色罗与安慰剂对胃食管反流病（GERD）患者唾液和食管保护因子的影响。
本研究为随机、双盲、安慰剂对照、交叉试验，38例GERD患者接受每日两次6mg替加色罗治疗或安慰剂治疗。在基础状态及咀嚼过程中采集唾液样本。此外，在32例GERD患者中，使用特制的食管导管，以连续方式在输注氯化钠、盐酸/胃蛋白酶和氯化钠期间采集唾液和食管分泌物。对唾液和食管灌洗液的pH值、体积、缓冲液含量、蛋白质、粘蛋白、表皮生长因子（EGF）、转化生长因子α（TGFα）和前列腺素E（PGE）2进行评估并进行统计学分析。
替加色罗给药期间的唾液流速高于基础状态（P <.01）和咀嚼期间的相应值（P <.001）。基础状态下（分别为P <.001和P <.01）和咀嚼期间（P <.05和P =.05）唾液碳酸氢盐和非碳酸氢盐缓冲液的分泌速率也增加。咀嚼期间唾液EGF增加（P <.05），而基础状态下PGE2和TGFα增加（P <.05和P <.01）。基础状态下替加色罗给药期间食管灌洗液体积增加（P <.05），而黏膜暴露于盐酸/胃蛋白酶并随后用氯化钠进行最终灌注后食管EGF分泌增加（P <.05）。
5-HT4激动剂对多种唾液保护因子以及食管EGF分泌有显著刺激作用，可能对GERD患者具有食管保护作用，并可能有助于未来探索新的治疗方法。
