Hollande F, Choquet A, Bali J P, Magous R
Laboratoire de Biochimie des Membranes, Faculté de Pharmacie, Montpellier, France.
Endocrinology. 1997 Mar;138(3):955-62. doi: 10.1210/endo.138.3.5006.
In this study we investigated the short-term effect of somatostatin on histamine synthesis in a cell population isolated from rabbit gastric mucosa and enriched in enterochromaffin-like cells. Somatostatin inhibited basal and gastrin-stimulated histamine synthesis through a dual mechanism involving a decrease in the affinity of histidine decarboxylase (HDC) for its substrate (L-histidine) and a reduction in the number of functional HDC molecules. H-89 (an inhibitor of cAMP-dependent protein kinase) mimicked somatostatin-induced reduction of HDC affinity, which, on the contrary, was selectively reversed by pertussis toxin (PTX). Furthermore, forskolin was shown to reverse the inhibitory effect of H-89 and to prevent the somatostatin-induced reduction in HDC affinity for L-histidine. Thus, the somatostatin-induced reduction in affinity seems to involve a PTX-sensitive G protein and an inhibition of the cAMP-dependent pathway. On the other hand, the somatostatin-induced decrease in the number of functional HDC molecules seems to be PTX insensitive and independent from a modulation of the cAMP pathway, and does not seem to involve a significant change in HDC messenger RNA expression or a regulation of protein kinase C. The exact nature of this second mechanism will need further studies to be elucidated.
在本研究中，我们调查了生长抑素对从兔胃黏膜分离出的、富含肠嗜铬样细胞的细胞群体中组胺合成的短期影响。生长抑素通过双重机制抑制基础和胃泌素刺激的组胺合成，这一机制包括组氨酸脱羧酶（HDC）对其底物（L-组氨酸）亲和力的降低以及功能性HDC分子数量的减少。H-89（一种环磷酸腺苷依赖性蛋白激酶抑制剂）模拟了生长抑素诱导的HDC亲和力降低，相反，百日咳毒素（PTX）可选择性逆转这种降低。此外，已证明福斯高林可逆转H-89的抑制作用，并防止生长抑素诱导的HDC对L-组氨酸亲和力的降低。因此，生长抑素诱导的亲和力降低似乎涉及一种对PTX敏感的G蛋白以及对环磷酸腺苷依赖性途径的抑制。另一方面，生长抑素诱导的功能性HDC分子数量减少似乎对PTX不敏感且独立于环磷酸腺苷途径的调节，并且似乎不涉及HDC信使核糖核酸表达的显著变化或蛋白激酶C的调节。第二种机制的确切性质需要进一步研究来阐明。
