胰高血糖素、胃抑肽和生长抑素与大鼠胃腺中存在的环磷酸腺苷生成系统的相互作用。

The interaction of glucagon, gastric inhibitory peptide and somatostatin with cyclic AMP production systems present in rat gastric glands.

作者信息

Gespach C, Bataille D, Dutrillaux M C, Rosselin G

出版信息

Biochim Biophys Acta. 1982 Feb 10;720(1):7-16. doi: 10.1016/0167-4889(82)90033-7.

Abstract

The effects of glucagon, gastric inhibitory peptide (GIP) and somatostatin on the generation of cyclic AMP have been studied under basal and histamine- or secretin-stimulated conditions in tubular gastric glands isolated by means of EDTA from the rat fundus and antrum. Four types of cell could be identified by electron microscopy; namely, parietal, mucous, peptic and some endocrine cells with a good morphological preservation of the cellular topography as seen in the intact mucosa. Immunoreactive somatostatin was found in antral glands (210 +/- 16 ng/g cell, wet wt., n = 9) as well as in fundic glands, but in smaller concentration (50 +/- 8 ng/g cell, wet wt., n = 9). (1) In rat fundic glands, glucagon, in supraphysiologic doses (3 . 10(-9) -5 . 10(-7) M), raised cyclic AMP levels 46 times above the basal. At maximally effective doses, combination of glucagon plus histamine was not additive whereas glucagon and secretin stimulations resulted in an additive response. Somatostatin (10(-10) -10(-7) M) inhibited both glucagon- and histamine-induced cyclic AMP production, whereas cimetidine specifically blocked the histaminergic stimulation. (2) In the same conditions, 10(-6)M glucagon produced a marginal effect (4-fold increase) in rat antrum, whereas GIP (10(-9) -10(-6)M) was unable to induce a significant rise of cyclic AMP production in either fundic or antral glands, or to prevent cyclic AMP production stimulated by histamine. (3) The present data do not support the view that circulating glucagon or GIP may regulate gastric secretion directly by a cyclic AMP-dependent mechanism in rat gastric glands and raise the possibility that gastric somatostatin may be the final mediator of the inhibitory actions of these hormones on acid secretion. (4) It is proposed that pancreatic glucagon acts through a receptor-cyclic AMP system which is specific for the bioactive peptide enteroglucagon ('oxyntomodulin'), probably in rat parietal cells.

摘要

已通过EDTA从大鼠胃底和胃窦分离出管状胃腺，研究了胰高血糖素、胃抑肽（GIP）和生长抑素在基础条件以及组胺或促胰液素刺激条件下对环磷酸腺苷（cAMP）生成的影响。通过电子显微镜可识别出四种类型的细胞，即壁细胞、黏液细胞、胃蛋白酶细胞以及一些内分泌细胞，其细胞形态结构保存良好，与完整黏膜中的情况相似。在胃窦腺（210±16 ng/g细胞，湿重，n = 9）以及胃底腺中均发现了免疫反应性生长抑素，但浓度较低（50±8 ng/g细胞，湿重，n = 9）。（1）在大鼠胃底腺中，超生理剂量（3×10⁻⁹ - 5×10⁻⁷ M）的胰高血糖素使cAMP水平比基础水平升高46倍。在最大有效剂量下，胰高血糖素加组胺的联合作用无相加效应，而胰高血糖素和促胰液素刺激则产生相加反应。生长抑素（10⁻¹⁰ - 10⁻⁷ M）抑制胰高血糖素和组胺诱导的cAMP生成，而西咪替丁特异性阻断组胺能刺激。（2）在相同条件下，10⁻⁶ M胰高血糖素在大鼠胃窦产生轻微作用（增加4倍），而GIP（10⁻⁹ - 10⁻⁶ M）在胃底腺或胃窦腺中均无法诱导cAMP生成显著增加，也不能阻止组胺刺激的cAMP生成。（3）目前的数据不支持循环中的胰高血糖素或GIP可能通过环磷酸腺苷依赖性机制直接调节大鼠胃腺分泌的观点，并增加了胃生长抑素可能是这些激素对胃酸分泌抑制作用的最终介质的可能性。（4）有人提出，胰腺胰高血糖素可能通过一种受体 - 环磷酸腺苷系统起作用，该系统对生物活性肽肠胰高血糖素（“胃泌酸调节素”）具有特异性，可能作用于大鼠壁细胞。