GASTRIN-RELEASING PEPTIDE-PREFERRING BOMBESIN BINDING-SITES IN HUMAN LUNG

Characterization of bombesin binding sites in healthy human lung was p erformed through direct binding techniques. There was limited binding in the absence of trypsin and chymotrypsin inhibitors, suggesting impo rtant activities of both enzymes in human lung and/or increased sensit ivity of the bombesin sites toward them. In human lung membranes, bomb esin, gastrin releasing peptide (GRP) and GRP-preferring bombesin rece ptor antagonists displaced [I-125-Tyr(4)]bombesin binding with high af finities (36-177 nM), whereas neuromedin B possessed a lower affinity of 2878 nM. [D-F(5)Phe(6),D-Ala(11)]bombesin-(6-13)-methyl ester, the most active GRP-preferring bombesin antagonist as yet reported, had th e highest affinity among all antagonists tested whereas neuromedin B h ad the lowest affinity. These data demonstrate that the bombesin bindi ng sites in the human lung are of the GRP-preferring type.