Gourlet P, De Neef P, Woussen-Colle M C, Vandermeers A, Vandermeers-Piret M C, Robberecht P, Christophe J
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Biochim Biophys Acta. 1991 Jul 22;1066(2):245-51. doi: 10.1016/0005-2736(91)90193-c.
Competition binding curves, using [125I-acetyl-His1]PACAP-27 as radioligand and dose-effect curves of adenylate cyclase activation in human SUP-T1 lymphoblastic membranes showed that PACAP-27 and PACAP-38 stimulate the enzyme through a single class of helodermin-preferring VIP receptors with the following order of potency: helodermin = [acetyl-His1]PACAP-27 greater than PACAP-38 greater than PACAP-27 greater than VIP. PACAP (6-27) (Ki 0.5-0.8 microM) and [Des-His1, Asn3]PACAP-27 (Ki 1-2 microM) acted as competitive antagonists. Using a series of 13 PACAP-27 analogues and fragments and three VIP analogues, we identified positions 1, 2, 3, 9 and 13 in PACAP-27 as being of importance for high-affinity binding. Thus, we added further evidence for considering that the present helodermin-preferring VIP receptors, when compared to a majority of VIP receptors and PACAP receptors, exhibit an original specificity pattern.
以[125I-乙酰组氨酸1]PACAP-27作为放射性配体的竞争结合曲线以及人SUP-T1淋巴细胞膜中腺苷酸环化酶激活的剂量效应曲线表明，PACAP-27和PACAP-38通过一类优先结合海蜥蜴毒素的VIP受体刺激该酶，其效力顺序如下：海蜥蜴毒素 = [乙酰组氨酸1]PACAP-27 > PACAP-38 > PACAP-27 > VIP。PACAP(6 - 27)(Ki 0.5 - 0.8微摩尔)和[去组氨酸1，天冬酰胺3]PACAP-27(Ki 1 - 2微摩尔)作为竞争性拮抗剂。使用一系列13种PACAP-27类似物和片段以及三种VIP类似物，我们确定了PACAP-27中的第1、2、3、9和13位对于高亲和力结合很重要。因此，我们进一步证明，与大多数VIP受体和PACAP受体相比，目前这种优先结合海蜥蜴毒素的VIP受体表现出一种独特的特异性模式。
