血管活性肠肽（VIP）对人喉癌细胞系HEp-2中环磷酸腺苷（cAMP）生成系统的激活作用。

Activation of the cAMP-generating system by vasoactive intestinal polypeptide (VIP) in the human laryngeal malignant cell line HEp-2.

作者信息

Prost A, Emami S, Rosselin G, Gespach C

出版信息

Biosci Rep. 1984 Dec;4(12):1045-50. doi: 10.1007/BF01116697.

Abstract

In the presence of 3-isobutyl-l-methylxanthine, VIP produced a dose-related (3 X 10(-9)-10(-7) M) increase (8-fold) in cAMP production in isolated HEp-2 cells incubated at 15 degrees C in KRP buffer. Among the peptides structurally related to VIP, including secretin (10(-7) M), pancreatic glucagon (10(-6) M), PHI, somatostatin-14 (10(-6) M), hpGRF (10(-8)-4 X 10(-6) M), GIP (2 X 10(-7) M), only PHI (3 X 10(-7) M and above) is able to activate the cAMP-generating system in HEp-2 cells, but at 10(2) times lower potency. Under the same conditions, histamine (10(-3) M) was also ineffective, while PGE2 (10(-7)-10(-4) M) increased (4-fold) basal cAMP levels in HEp-2 cells. The VIP effect is related to the interaction of the peptide on VIP recognition sites (125I-VIP-binding capacity), coupled to the membrane-bound adenylate cyclase. The results indicate that the transformed laryngeal cell line HEp-2 possesses a receptor-cAMP system preferentially activated by VIP (relative potencies: VIP greater than PHI much greater than other peptides of the secretin family), and suggest that this neuropeptide could modulate biological functions in normal laryngeal epithelia in man.

摘要

在3-异丁基-1-甲基黄嘌呤存在的情况下，血管活性肠肽（VIP）在KRP缓冲液中于15℃孵育的分离的HEp-2细胞中使环磷酸腺苷（cAMP）生成量呈剂量相关（3×10⁻⁹ - 10⁻⁷ M）增加（8倍）。在与VIP结构相关的肽中，包括促胰液素（10⁻⁷ M）、胰高血糖素（10⁻⁶ M）、肽组氨酸异亮氨酸（PHI）、生长抑素-14（10⁻⁶ M）、人胰高血糖素释放因子（hpGRF，10⁻⁸ - 4×10⁻⁶ M）、胃抑肽（GIP，2×10⁻⁷ M），只有PHI（3×10⁻⁷ M及以上）能够激活HEp-2细胞中的cAMP生成系统，但效力低100倍。在相同条件下，组胺（10⁻³ M）也无作用，而前列腺素E2（PGE2，10⁻⁷ - 10⁻⁴ M）使HEp-2细胞中的基础cAMP水平增加（4倍）。VIP的作用与该肽在VIP识别位点（¹²⁵I-VIP结合能力）上的相互作用有关，该位点与膜结合的腺苷酸环化酶偶联。结果表明，转化的喉癌细胞系HEp-2具有优先被VIP激活的受体-cAMP系统（相对效力：VIP＞PHI＞＞促胰液素家族的其他肽），并提示这种神经肽可能调节人正常喉上皮中的生物学功能。