Gourlet P, Vertongen P, Vandermeers A, Vandermeers-Piret M C, Rathe J, De Neef P, Waelbroeck M, Robberecht P
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Brussels, Belgium.
Peptides. 1997;18(3):403-8. doi: 10.1016/s0196-9781(96)00322-1.
RO 25-1553 is a synthetic VIP analogue that induced a long-lasting relaxation of tracheal and bronchial smooth muscles as well as a reduction of edema and eosinophilic mobilization during pulmonary anaphylaxis. In the present study, we tested in vitro the capacity of RO 25-1553 to occupy the different VIP/PACAP receptor subclasses and to stimulate adenylate cyclase activity. The cellular models tested expressed one single receptor subtype: Chinese hamster ovary (CHO) cells transfected with the rat recombinant PACAP I, rat VIP1, and human VIP2 receptors; SUP T1 cells expressing the human VIP2 and HCT 15 and LoVo cells expressing the human VIP1 receptor. RO 25-1553 was threefold more potent than VIP on the human VIP2 receptor, 100- and 600-fold less potent than VIP on the rat and human VIP1 receptors, respectively, and 10-fold less potent than VIP and 3000-fold less potent than PACAP on the PACAP I receptor. RO 25-1553 was a full agonist on the VIP2, the PACAP I, and the rat recombinant VIP1 receptor but a partial agonist only on the human VIP1 receptor. Thus, RO 25-1553 is a highly selective agonist ligand for the VIP2 receptor subclass.
RO 25-1553是一种合成的血管活性肠肽（VIP）类似物，可使气管和支气管平滑肌产生持久舒张，并在肺部过敏反应中减轻水肿和嗜酸性粒细胞动员。在本研究中，我们在体外测试了RO 25-1553占据不同VIP/垂体腺苷酸环化酶激活肽（PACAP）受体亚型以及刺激腺苷酸环化酶活性的能力。所测试的细胞模型表达单一受体亚型：用大鼠重组PACAP I、大鼠VIP1和人类VIP2受体转染的中国仓鼠卵巢（CHO）细胞；表达人类VIP2的SUP T1细胞以及表达人类VIP1受体的HCT 15和LoVo细胞。RO 25-1553对人类VIP2受体的效力比VIP高两倍，对大鼠和人类VIP1受体的效力分别比VIP低100倍和600倍，对PACAP I受体的效力比VIP低10倍，比PACAP低3000倍。RO 25-1553对VIP2、PACAP I和大鼠重组VIP1受体是完全激动剂，但对人类VIP1受体只是部分激动剂。因此，RO 25-1553是VIP2受体亚型的高度选择性激动剂配体。
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