Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms.
Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms.
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犬肠内分泌细胞的生长抑素和毒蕈碱抑制：细胞机制。
DOI：
10.1152/ajpgi.1987.253.5.g684
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Soll,AH
中科院分区：
文献类型：
--
作者：
Barber,DL;Gregor,M;Soll,AH
利用新近建立的犬原代肠内分泌细胞培养系统，研究了环磷酸腺苷（cAMP）在神经降压素和肠胰高血糖素释放中的作用。肾上腺素刺激的肽释放伴随着cAMP积累的增加。卡巴胆碱和生长抑素（SRIF）显着抑制肾上腺素对肽释放和cAMP含量的影响。3-异丁基-1-甲基黄嘌呤的加入增强肾上腺素刺激肽的释放，而不改变卡巴胆碱和SRIF的相对抑制作用，表明这些药物不会通过增加磷酸二酯酶活性来抑制内分泌细胞功能。为了确定cAMP产生在介导肽释放的抑制中的作用，将细胞与细菌毒素百日咳毒素（PT）孵育。在用PT预处理的培养物中，卡巴胆碱对肽释放和cAMP积累的抑制被完全逆转。相比之下，SRIF抑制cAMP含量被完全逆转PT治疗后，但抑制肽释放仅部分逆转。此外，毒素处理仅部分逆转了毛喉素和钙离子载体刺激肽释放的SRIF抑制。这些数据表明，毒蕈碱胆碱能抑制神经降压素和肠胰高血糖素的释放是完全通过介导的鸟嘌呤核苷酸结合蛋白（Ni）或类似的毒素敏感，GTP结合蛋白。SRIF抑制的肽释放部分通过毒素敏感性底物介导，如降低的cAMP水平的PT逆转所证明的。SRIF还可以通过不与Ni或类似的PT敏感性GTP结合蛋白偶联的cAMP非依赖性途径抑制神经降压素和肠胰高血糖素释放。
Using a recently developed canine primary enteric endocrine cell culture system, we have investigated the role of adenosine 3',5'-cyclic monophosphate (cAMP) in mediating the release of neurotensin and enteroglucagon. Epinephrine-stimulated peptide release was concomitant with an increase in cAMP accumulation. Carbachol and somatostatin (SRIF) markedly inhibited the epinephrine effect on both peptide release and cAMP content. The addition of 3-isobutyl-1-methylxanthine potentiated epinephrine-stimulated peptide release without altering the relative inhibition by carbachol and SRIF, suggesting that these agents did not inhibit endocrine cell function by increasing phosphodiesterase activity. To determine the role of cAMP production in mediating inhibition of peptide release, cells were incubated with the bacterial toxin, pertussis toxin (PT). In cultures pretreated with PT, carbachol inhibition of both peptide release and cAMP accumulation was completely reversed. In contrast, SRIF inhibition of cAMP content was completely reversed after PT treatment, but inhibition of peptide release was only partially reversed. Additionally, toxin treatment only partially reversed SRIF inhibition of forskolin- and calcium ionophore-stimulated peptide release. These data suggest that muscarinic cholinergic inhibition of neurotensin and enteroglucagon release is mediated entirely through the guanine nucleotide-binding protein (Ni) or a similar toxin-sensitive, GTP-binding protein. SRIF-inhibited peptide release is mediated partially through a toxin-sensitive substrate, as evidenced by PT reversal of reduced cAMP levels. SRIF may also inhibit neurotensin and enteroglucagon release by a cAMP-independent pathway that is not coupled to Ni or a similar PT-sensitive, GTP-binding protein.