| Autor: |
Heimbrook, D C, Saari, W S, Balishin, N L, Friedman, A, Moore, K S, Reimen, M W, Kiefer, D M, Rotberg, N S, Wallen, J W, Oliff, A |
| Zdroj: |
Journal of Biological Chemistry; July 1989, Vol. 264 Issue: 19 p11258-11262, 5p |
| Abstrakt: |
Gastrin releasing peptide (GRP) is a 27-residue peptide hormone which is analogous to the amphibian peptide bombesin. GRP serves a variety of physiological functions and has been implicated as an autocrine factor in the growth regulation of small cell lung cancer cells. We have developed a series of potent GRP antagonists by modification of the COOH terminus of N-acetyl-GRP-20–27. The most potent member of this series, N-acetyl-GRP-20–26-OCH2CH3, exhibits an IC50of 4 nMin a competitive binding inhibition assay. This compound blocks GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts, inhibits GRP-dependent release of gastrin in vitro, and blocks GRP-induced elevation of [Ca2+]iin H345 small cell lung cancer cells. These results demonstrate that while residues 20–27 of GRP influence binding of the parent peptide to its receptor, the COOH-terminal amino acid is primarily responsible for triggering the subsequent biological response. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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