Pozo D, Guerrero J M, Calvo J R
Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Spain.
Peptides. 1995;16(2):313-8. doi: 10.1016/0196-9781(94)00192-8.
In the present study, we examined the effect of pretreatment with VIP and various peptides structurally related to VIP such us PHI, helodermin, and secretin on VIP receptor number and affinity, as well as VIP-stimulated cyclic AMP production in rat peritoneal macrophages. Short-term (5-30 min) exposures of rat peritoneal macrophages to 0.1 microM VIP induced a rapid reduction in specific binding. Pretreatment for 15 and 30 min caused 26% (SEM = 6) and 48% (SEM = 4) reduction in specific binding, respectively. The maximal effect was observed at 120 min, causing a decrease of 67% (SEM = 6) in specific binding. Pretreatment with 0.1 microM VIP for 15, 30, and 120 min caused 23% (SEM = 9), 52% (SEM = 4), and 76% (SEM = 4) reduction in cyclic AMP production, respectively. Only VIP concentrations at the nanomolar level and higher were shown to be effective. The potency of VIP and related peptides to desensitize was similar to their potency to occupy receptors and to activate cyclic AMP production. The internalization of radioiodinated VIP was also studied. It was shown that receptor-bound ligand is internalized during the downregulation process. However, the diminution in VIP binding to macrophages was not completely explained by internalization.
在本研究中，我们检测了用血管活性肠肽（VIP）以及与VIP结构相关的各种肽（如胰高血糖素样肽I、胃泌素释放肽、促胰液素）预处理对大鼠腹腔巨噬细胞中VIP受体数量、亲和力以及VIP刺激的环磷酸腺苷（cAMP）生成的影响。将大鼠腹腔巨噬细胞短期（5 - 30分钟）暴露于0.1微摩尔/升的VIP会导致特异性结合迅速减少。预处理15分钟和30分钟分别使特异性结合减少26%（标准误 = 6）和48%（标准误 = 4）。在120分钟时观察到最大效应，特异性结合减少了67%（标准误 = 6）。用0.1微摩尔/升的VIP预处理15分钟、30分钟和120分钟分别使cAMP生成减少23%（标准误 = 9）、52%（标准误 = 4）和76%（标准误 = 4）。只有纳摩尔及更高浓度的VIP才显示出有效。VIP及相关肽脱敏的效力与其占据受体和激活cAMP生成的效力相似。还研究了放射性碘化VIP的内化情况。结果表明，在下调过程中受体结合的配体发生内化。然而，巨噬细胞上VIP结合的减少并不能完全用内化来解释。
