Bile acid increases expression of the histamine-producing enzyme,histidine decarboxylase,in gastric cells

AIM:To investigate the effect of bile acid on the expression of histidine decarboxylase(HDC),which is a major enzyme involved in histamine production,and gene expression of gastric transcription factors upon cooperative activation.METHODS:HDC expression was examined by immunohistochemistry,reverse transcriptase polymerase chain reaction,and promoter assay in human gastric precancerous tissues,normal stomach tissue,and gastric cancer cell lines.The relationship between gastric precancerous state and HDC expression induced by bile acid was determined.The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated.MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor(FXR),small heterodimer partner(SHP),and caudal-type homeodomain transcription factor(CDX)1 expression plasmids.The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay.RESULTS:Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases.Here,we show that bile acid increased the expression of HDC,which is a rate-limiting enzyme of the histamine production pathway.FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression.In addition,the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression.We confirmed similar expression patterns for HDC,CDX1,and SHP in patient tissues.CONCLUSION:HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR,SHP,and CDX1.

脑内组胺对戊四唑慢性癫痫形成过程的作用机制

目的 :探讨组胺对戊四唑诱发慢性癫痫形成的作用机制。方法 :大鼠隔日腹腔注射亚惊厥剂量的戊四唑( 35 mg/ kg)诱发化学点燃癫痫。观察每次戊四唑注射后 30 min内的癫痫发作行为变化。结果 :腹腔内注射组氨酸或侧脑室内注射 clobenpropit都能剂量依赖性地延缓癫痫的形成 ,表现为延长肌性痉挛、阵挛性癫痫全身性发作的反应潜伏时间及抑制癫痫发作的级别。 H3 受体激动剂 immepip和组氨酸脱羧酶抑制剂α-氟甲基组氨酸剂量依赖性地抑制 clobenpropit的抗癫痫作用。结论 :脑内组胺在对抗阵挛性癫痫发作中起较重要的作用 ,其作用主要与

内源性组胺经突触前组胺H_3受体介导抑制心交感神经冲动传递

采用豚鼠离体右心房标本观察内源性组胺对心交感神经冲动传递的影响。以组氨酸１ｕｍｏｌ·Ｌ￣（－１）温育右心房标本以增加心肌组胺的合成，１ｈ后施以电场刺激。心房肌正性变力效应较正常降低２６％。雷尼替丁（１ｕｍｏｌ·Ｌ￣（－１））和氯苯吡胺（１ｐｍｏｌ·Ｌ￣（－１））对上述抑制效应无影响。Ｈ＿３受体拮抗剂布立马胺可浓度依赖性地拮抗上述效应。Ｈ＿３受体激动剂（Ｒ）－ａ－甲基组胺则可抑制布立马胺的作用用肥大细胞脱颗粒剂化合物４８－８０温育标本１５ｍｈ。可使电场刺激诱发的正性变力效应增强７５％。结果提示。内源性组胺可能通过交感神经末梢突触前膜组胺Ｈ＿３受体，参予去甲肾上腺素释放的负调节。

组胺H_3受体定位于心交感神经末梢突触前膜的进一步证明

目的：观察［￣３Ｈ］组胺在心肌细胞粗制膜上的结合情况．方法：制备心肌细胞粗制膜，将膜制备与［￣３Ｈ］组胺在３７℃下共同孵育３０ｍｉｎ，然后将孵育液经玻璃纤维膜减压抽滤．滤膜烘干后放入闪烁瓶中，记录放射活性．结果：选择性Ｈ－３受体激动剂α－甲基组胺（α－ＭｅＨＡ，１μｍｏｌ／Ｌ）可竞争性抑制［￣３Ｈ］组胺在心肌膜制备上的特异性结合，［￣３Ｈ］组胺（０．５和１ ｎｍｏｌ／Ｌ）特异性结合量减少至对照值的６４．１±１１．１％和６０．５１±４．１％。６－羟基多巴胺（６－ＯＨＤＡ）化学切割交感神经后，可以使［￣３Ｈ］组胺与膜受体的结合量减少至对照值的７７．３±６．９％和８０．１±６．９％．在化学去交感神经的膜制备中，α－ＭｅＨＡ仅轻度降低组胺与膜受体的特异性结合量．结论：化学法切除交感神经后，丢失了一部分与［￣３Ｈ］组胺结合的受体蛋白，这部分定位于交感神经末梢的组胺受体，可以被α－ＭｅＨＡ竞争性结合，属于组胺Ｈ－３受体．