A human melanoma‐derived cell line (IGR39) with a very high number of vasoactive‐intestinal‐peptide (VIP) receptors

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Abstract
Vasoactive intestinal peptide (VIP) stimulated in a dose-dependent manner the accumulation of cAMP in human melanoma-derived cell line IGR39. The maximal effect (about 100 times times the basal level) was observed with 10 nM VIP. Half-maximum cAMP production was obtained at 0.78 nM. VIP-related peptides were also potent in stimulating the cAMP production in IGR39 cells. The order of potency was VIP .mchgt. peptide histidine-methioninamide > human growth-hormone-releasing factor(1-44) > secretin > glucagon. Using the same conditions, IGR37 cells, a metastatic counterpart of IGR39 cells, displayed a weak stimulation of cAMP production. After exposure of IGR39 cells to 10 nM VIP, the cAMP response to a new stimulation by VIP was strongly reduced. This desensitization of IGR39 cells to VIP was rapid (t12 < 2 min) and homologous. Preincubation of IGR39 cells in the presence of native VIP induced disappearance of the VIP-binding sites at the cell suface. This phenomenon was dependent on time and VIP concentration. Maximum effect (loss of 80% of binding capacity) was obtained after exposure of the cells at 37.degree. C with a VIP concentration of 1 .mu.M. The t1/2 of maximum disappearance was less than 2 min and the concentration of VIP giving half-maximum decrease in binding of mono[125]iodinated VIP (125I-VIP) was 8 nM. This phenomenon was also reversible since 85% of the VIP-binding capacity could be restored in less than 1 h by incubating IGR39 cells in a VIP-free medium. The IGR39 cell line should be a useful model for further study of the structure and function of the human VIP receptor.