Oikawa Y
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1993 Sep;68(5):683-93.
Intracellular mechanisms of receptor-mediated acid secretion and potentiating interactions of receptors were explored in isolated gastric glands obtained from the stomach of New Zealand White rabbits. Intracellular free calcium concentration ([Ca2+]i) was measured by a digitized video-image analysis with a dual-wavelength excitation microspectrofluorometry in fura-2 loaded parietal cells, and acid secretion was determined in parallel experiments by monitoring the accumulation of [14C] aminopyrine (AP) in suspension of isolated glands. Histamine and carbachol stimulated acid secretion and increased [Ca2+]i in a concentration-dependent manner. The concentration-response curve for the acid producing effect of carbachol was overlapped by that for the [Ca2+]i-increasing effect. However, the concentration-response curve for the [Ca2+]i-increasing effect of histamine was shifted by approximately one order from that for the acid-producing effect, indicating that a low concentration of histamine can also stimulate acid secretion without [Ca2+]i increase in the rabbit parietal cells. Cimetidine, a H2-blocker, inhibited the histamine-induced acid secretion and [Ca2+]i increase competitively, and those responses induced by carbachol non-competitively. Carbachol at a concentration of 10(-3)M did not affect the histamine concentration of solution containing isolated gastric glands. Neither 10(-6)M 3-isobutyl-1-methyl-xanthine (IBMX) nor 3 x 10(-5)M dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) affected AP uptake and [Ca2+]i per se. However, these agents significantly potentiated the carbachol-induced acid secretion and [Ca2+]i increase. These results suggest that tonic stimulation of H2-receptors by a small amount of endogenous histamine potentiates the cholinergic acid secretion and [Ca2+]i increase. Parietal cells preconditioned by a small increase in intracellular cAMP may easily increase [Ca2+]i and acid secretion in response to cholinergic stimulation.
利用从新西兰白兔胃中获取的分离胃腺，探讨了受体介导的酸分泌的细胞内机制以及受体的增强相互作用。通过双波长激发显微荧光分光光度法的数字化视频图像分析，在负载fura-2的壁细胞中测量细胞内游离钙浓度（[Ca2+]i），并在平行实验中通过监测[14C]氨基比林（AP）在分离腺体制剂中的积累来测定酸分泌。组胺和卡巴胆碱刺激酸分泌，并以浓度依赖性方式增加[Ca2+]i。卡巴胆碱产酸作用的浓度-反应曲线与[Ca2+]i增加作用的曲线重叠。然而，组胺增加[Ca2+]i作用的浓度-反应曲线相对于产酸作用的曲线大约偏移了一个数量级，表明低浓度的组胺也可在兔壁细胞中不增加[Ca2+]i的情况下刺激酸分泌。H2受体阻滞剂西咪替丁竞争性抑制组胺诱导的酸分泌和[Ca2+]i增加，而非竞争性抑制卡巴胆碱诱导的这些反应。浓度为10(-3)M的卡巴胆碱不影响含有分离胃腺的溶液中的组胺浓度。10(-6)M的3-异丁基-1-甲基黄嘌呤（IBMX）和3×10(-5)M的二丁酰腺苷3',5'-环一磷酸（dbcAMP）本身均不影响AP摄取和[Ca2+]i。然而，这些药物显著增强了卡巴胆碱诱导的酸分泌和[Ca2+]i增加。这些结果表明，少量内源性组胺对H2受体的紧张性刺激增强了胆碱能酸分泌和[Ca2+]i增加。细胞内cAMP少量增加预处理的壁细胞可能更容易响应胆碱能刺激而增加[Ca2+]i和酸分泌。
