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 mumol/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 mumol/l 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 psi-leucine bond [D-Phe6-psi-Leu13-D-Cpa14-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-phenylalanine 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.
Buchan
A M
AM
Department of Physiology, University of British Columbia, Vancouver, Canada.
Meloche
M
M
Coy
D H
DH
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D011706:Pyloric Antrum / Q000166:cytology / Q000187:drug effects; D011863:Radioimmunoassay
D005755:Gastrins; D001839:Bombesin