Sandvik A K, Kleveland P M, Waldum H L
Dept. of Medicine, Trondheim University, Norway.
Scand J Gastroenterol. 1988 Nov;23(9):1049-56. doi: 10.3109/00365528809090168.
The present study examines the role of histamine in the stimulation of acid secretion induced by vagal nerve stimulation and by the muscarinic M1 agonist McN-A-343 in the totally isolated, vascularly perfused rat stomach. The stimuli were combined with an agent stimulating the cAMP system (isobutyl methylxanthine (IMX) or forskolin), a muscarinic antagonist (atropine or pirenzepine), or a histamine H2 antagonist (ranitidine). IMX and forskolin potentiated McN-A-343-stimulated acid secretion, yielding acid outputs of 280% and 260% of the sum of McN-A-343- and IMX-, or McN-A-343- and forskolin-stimulated outputs, respectively. Ranitidine inhibited acid secretion stimulated by McN-A-343 alone or in combination with IMX, whereas the forskolin-stimulated secretion was not influenced by the H2 antagonist. This strongly indicates that endogenous histamine potentiates muscarinic M1-stimulated acid secretion by increasing parietal cell cAMP. Vagal nerve stimulation with IMX increased acid output from 12.2 +/- 3.0 to 49.2 +/- 9.3 mumol/60 min (mean +/- SEM). The M1 antagonist pirenzepine and the M1/M2 antagonist atropine both significantly (p less than 0.01) inhibited vagally stimulated acid secretion. Histamine output as measured in the venous effluent was unchanged by McN-A-343, whereas nerve stimulation induced a clear increase in venous histamine output, from 101 +/- 21 before to 212 +/- 28 pmol/min (mean +/- SEM) after initiation of nerve stimulation. Histamine release was reduced to base-line levels by atropine but only insignificantly inhibited by pirenzepine, indicating a muscarinic M2 stimulation of histamine release in the rat stomach.
本研究考察了组胺在完全分离、血管灌流的大鼠胃中对迷走神经刺激和毒蕈碱M1激动剂McN - A - 343诱导的胃酸分泌刺激中的作用。刺激与刺激环磷酸腺苷（cAMP）系统的药物（异丁基甲基黄嘌呤（IMX）或福斯可林）、毒蕈碱拮抗剂（阿托品或哌仑西平）或组胺H2拮抗剂（雷尼替丁）联合使用。IMX和福斯可林增强了McN - A - 343刺激的胃酸分泌，酸分泌量分别为McN - A - 343与IMX或McN - A - 343与福斯可林刺激分泌量之和的280%和260%。雷尼替丁抑制单独使用McN - A - 343或与IMX联合使用时刺激的胃酸分泌，而福斯可林刺激的分泌不受H2拮抗剂影响。这有力地表明内源性组胺通过增加壁细胞cAMP来增强毒蕈碱M1刺激的胃酸分泌。迷走神经刺激联合IMX使酸分泌量从12.2±3.0增加到49.2±9.3 μmol/60分钟（平均值±标准误）。M1拮抗剂哌仑西平和M1/M2拮抗剂阿托品均显著（p＜0.01）抑制迷走神经刺激的胃酸分泌。McN - A - 343对静脉流出液中组胺分泌量无影响，而神经刺激导致静脉组胺分泌量明显增加，从神经刺激开始前的101±21增加到刺激后的212±28 pmol/分钟（平均值±标准误）。阿托品使组胺释放降至基线水平，但哌仑西平仅轻微抑制，表明毒蕈碱M2刺激大鼠胃中的组胺释放。
