Ottaway C A
Department of Medicine, University of Toronto, Canada.
J Neuroimmunol. 1992 Jul;39(1-2):49-56. doi: 10.1016/0165-5728(92)90173-i.
The effect of sulfhydryl-containing compounds on the specific binding of the neuropeptide vasoactive intestinal peptide (VIP) to murine lymphocytes was studied. Both 2-mercaptoethanol (2ME) and dithiothreitol (DTT) inhibited VIP-binding to lymphocytes at millimolar concentrations. A sulfhydryl-containing analogue of VIP, [Cys2]VIP, was synthesized. This compound competed for the binding of [125I]VIP about 150,000 x more effectively than 2ME, but was approximately 100 x less effective than VIP itself. Both VIP and [Cys2]VIP increased intracellular cyclic AMP and inhibited the proliferative response of lymphocyte cultures to concanavalin A (ConA), but the molar potency of [Cys2]VIP on these lymphocyte activities was approximately 100 x less than that of VIP. The effects of VIP and [Cys2]VIP on intracellular cyclic AMP and ConA-stimulated proliferation were competed for by the VIP receptor antagonist [4Cl-D-Phe6,Leu17]VIP. Replacement of serine2 with L-cysteine disrupts the ability of VIP to occupy and activate lymphocyte VIP receptors. This may reflect a role of serine2 in hydrogen-bond formation during ligand-receptor interactions, or a functional role of sulfhydryl-containing residues of the VIP receptor in maintaining the integrity of the binding site of the VIP receptor on lymphocytes.
研究了含巯基化合物对神经肽血管活性肠肽（VIP）与小鼠淋巴细胞特异性结合的影响。2-巯基乙醇（2ME）和二硫苏糖醇（DTT）在毫摩尔浓度下均抑制VIP与淋巴细胞的结合。合成了一种含巯基的VIP类似物[Cys2]VIP。该化合物竞争[125I]VIP结合的能力比2ME有效约150,000倍，但比VIP本身的效力约低100倍。VIP和[Cys2]VIP均增加细胞内环状AMP并抑制淋巴细胞培养物对伴刀豆球蛋白A（ConA）的增殖反应，但[Cys2]VIP对这些淋巴细胞活性的摩尔效力比VIP约低100倍。VIP受体拮抗剂[4Cl-D-Phe6，Leu17]VIP可竞争VIP和[Cys2]VIP对细胞内环状AMP和ConA刺激增殖的影响。将丝氨酸2替换为L-半胱氨酸会破坏VIP占据和激活淋巴细胞VIP受体的能力。这可能反映了丝氨酸2在配体-受体相互作用过程中氢键形成中的作用，或者VIP受体含巯基残基在维持淋巴细胞上VIP受体结合位点完整性方面的功能作用。
