Maxadilan interacts with receptors for pituitary adenylyl cyclase activating peptide in human SH-SY5Y and SK-N-MC neuroblastoma cells

Maxadilan interacts with receptors for pituitary adenylyl cyclase activating peptide in human SH-SY5Y and SK-N-MC neuroblastoma cells
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DOI:
10.1054/npep.1999.0004
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发表时间:
1999-04-01
期刊:
影响因子:
2.9
通讯作者:
Muff, R
Muff, R
中科院分区:
医学3区
文献类型:
--
作者:
Eggenberger, M;Born, W;Muff, R

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垂体腺苷酸环化酶激活肽(PACAP)受体已在人SH-SY5Y神经母细胞瘤细胞中被鉴定出来,在[I-125]PACAP结合抑制和刺激cAMP积累方面,PACAP比血管活性肠肽(VIP)强1000倍。来自沙蝇长掌Lutzomyia longipalpis唾液腺的血管扩张肽Maxadilan也特异性结合SH-SY5Y细胞,并与PACAP在[I-125]PACAP和[I-125] Maxadilan结合抑制和刺激cAMP积累方面具有同等作用。麦克沙迪兰和PACAP均能提高胞质游离钙浓度。在人SK-N-MC神经母细胞瘤细胞中,PACAP、VIP和maxadilan等量刺激cAMP的积累。VIP和maxadilan的最大作用是叠加的,达到PACAP单独使用的效果。在人T47D乳腺癌细胞中,PACAP和VIP在刺激cAMP积累方面也具有同等效力,而maxadilan则无活性。结果与maxadilan与SH-SY5Y细胞中PACAP特异性PAC(1)受体的相互作用一致,而与VPAC受体的相互作用不一致,在T47D细胞中VIP和PACAP没有区别。此外,maxadilan是PAC(1)受体特异性激动剂,可以在SK-N-MC细胞中区分共表达的PAC(1)和VPAC受体。
Receptors for pituitary adenylyl cyclase activating peptide (PACAP) have been identified in human SH-SY5Y neuroblastoma cells with PACAP being 1000-fold more potent than vasoactive intestinal peptide (VIP) in [I-125]PACAP binding inhibition and stimulation of cAMP accumulation. Maxadilan, a vasodilator peptide from the salivary gland of the sand fly Lutzomyia longipalpis also specifically bound to SH-SY5Y cells, and was equipotent to PACAP in [I-125]PACAP and [I-125]maxadilan binding inhibition, and stimulation of cAMP accumulation. Maxadilan and PACAP also increased the cytosolic free calcium concentration. in human SK-N-MC neuroblastoma cells PACAP, VIP and maxadilan equipotently stimulated cAMP accumulation. The maximal effects of VIP and maxadilan were additive and reached those of PACAP alone. In human T47D breast carcinoma cells PACAP and VIP were also equipotent in the stimulation of cAMP accumulation, but maxadilan was inactive. The results are consistent with the interaction of maxadilan with PACAP specific PAC(1) receptors in SH-SY5Y cells, but not with VPAC receptors, not differentiating between VIP and PACAP in T47D cells. Moreover, maxadilan is a PAC(1) receptor specific agonist which allows discrimination of co-expressed PAC(1) and VPAC receptors in SK-N-MC cells.