High-affinity receptors for peptides of the bombesin family in Swiss 3T3 cells.
Gastrin-releasing peptide (GRP) labeled with 125I at tyrosine-15 (125I-GRP) binds to intact quiescent Swiss 3T3 cells in a specific and saturable manner. Scatchard analysis indicates the presence of a single class of high-affinity binding sites of Kd = 0.5 X 10(-9) M and a value for the number of sites per cell of about 100,000. 125I-GRP binding was not inhibited by other mitogens for these cells, and cell lines that are mitogenically unresponsive to GRP do not exhibit specific GRP binding. Structure-activity relationships show a close parallel between the ability of a range of GRP-related peptides to both inhibit GRP binding and to stimulate mitogenesis. Further, GRP binding is selectively blocked in a competitive fashion by a novel bombesin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11] substance P. In addition, this compound selectively inhibits GRP and bombesin-induced mitogenesis. These results demonstrate that the mitogenic response of Swiss 3T3 cells to peptides of the bombesin family is mediated by a class of receptors distinct from those of other mitogens for these cells.
D000818:Animals; D001839:Bombesin / Q000037:antagonists & inhibitors; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D019886:Gastrin-Releasing Peptide; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D018004:Receptors, Bombesin; D011956:Receptors, Cell Surface / Q000032:analysis*
D007457:Iodine Radioisotopes; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D018004:Receptors, Bombesin; D011956:Receptors, Cell Surface; D019886:Gastrin-Releasing Peptide; D004247:DNA; D001839:Bombesin