A structure function study of C-terminal extensions of bombesin

Peptides. 1991 Sep-Oct;12(5):1149-51. doi: 10.1016/0196-9781(91)90072-w.

Abstract

Synthetic C-terminal extensions of BN were synthesized and the biological potency evaluated using Swiss 3T3 and small cell lung cancer cells. BN, which has an amidated C-terminal, inhibited specific [125I-Tyr4]BN binding activity to Swiss 3T3 cells with an IC50 value of 1 nM, whereas the IC50 of BN-OH, which has a free C-terminal, was 1800 nM. The IC50 values of BNG, BNGK and BNGKK were 1400, 4700 and 500 nM, respectively. Similar binding data were obtained using SCLC cell line NCI-H345 and the bombesin analogues functioned as agonists based on the ability to elevate cytosolic Ca2+ in Fura-2 AM loaded SCLC cells. Also, the bombesin analogues stimulated 3H-thymidine uptake in Swiss 3T3 cells and the ED50 values for BN, BNG, BNGK and BNGKK were 1, 1300, 3900 and 400 nM. These data suggest that an amidated C-terminal is essential for high affinity binding and potency of BN.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding, Competitive
  • Bombesin / analogs & derivatives*
  • Bombesin / chemical synthesis
  • Bombesin / metabolism*
  • Bombesin / pharmacology
  • Calcium / metabolism
  • Carcinoma, Small Cell
  • Cell Line
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Humans
  • Kinetics
  • Lung Neoplasms
  • Mice
  • Receptors, Bombesin
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / metabolism*

Substances

  • Receptors, Bombesin
  • Receptors, Neurotransmitter
  • Bombesin
  • Calcium