INHIBITION OF BOMBESIN-STIMULATED GASTRIN-RELEASE FROM ISOLATED HUMAN G-CELLS BY BOMBESIN ANALOGS

This study investigated the ability of 6 putative bombesin (BN) antagonists to inhibit BN-stimulated gastrin release from human antral G cells maintained in culture for 48 h. The analogs studied comprised different sequence changes based around a constant 6-amino-acid sequence from the C-terminal of the peptide. At concentrations of 1.0 (µmol/l, analogs 1 and 2 stimulated gastrin release 3-fold above basal. The remaining 4 analogs showed no agonistic activity. After the addition of concentrations of 1.0 µmol/1 against a BN concentration of 10.0 nmol/l the following levels of inhibition were obtained: analog 3. 90 ± 1.4%; analog 4, 95 ± 0.5%; analog 5, 99 ± 2.4%, and analog 6. 85 ± 3.8%. The 2 most effective analogs were analog 3, which was 9 amino acids in length with substitutions of two D-phenylalanine residues and a ψ-leucine bond [D-Phef6-ψ-Leu13-D-Cpal4-BN(6-14)NH2],and analog 5, which was 8 amino acids in length with a methyl ester at the C-terminus and a single D-phenyialanine substitution at the N-terminus [D-Phe6-BN(6-13)OMe]. These results suggest that the BN receptor present on the human antral G cells differs from that on guinea pig acinar cells and canine G cells, being less sensitive to C-terminal structural modifications. © 1990 S. Karger AG, Basel.