Effects of imidazoline binding site ligands on the growth and viability of clonal pancreatic β-cells

Mourtada, M.; Elliott, J.; Smith, S.A.; Morgan, N.G.

Abstract

Pancreatic β-cells express imidazoline binding sites which play a role in the regulation of insulin secretion, but it is not known whether ligands for these sites also affect other aspects of β-cell physiology. In the present study, we have investigated the effects of a range of imidazoline reagents on the growth and viability of clonal pancreatic β-cells (RINm5F and HIT-T15). Three imidazoline compounds (idazoxan, phentolamine and antazoline) were found to cause marked inhibition of β-cell growth in a time and concentration dependent manner. Idazoxan was the most potent of these with as little as 0.5 µM causing a significant decrease in β-cell viability (EC50 ~10 µM). All three imidazolines also decreased the viability of clonal β-cells in parallel with their inhibitory effects on cell growth. These effects were not reproduced by any of a wide-range of other imidazoline compounds, including effective insulin secretagogues such as efaroxan and RX821002. The effects of the three ligands did not correlate with their relative potencies for binding to any of the well-characterised imidazoline binding sites nor to α2-adrenoceptors. In addition, the inhibitory responses were not antagonised by other imidazoline binding site ligands.

Citation

Mourtada, M., Elliott, J., Smith, S., & Morgan, N. (2000). Effects of imidazoline binding site ligands on the growth and viability of clonal pancreatic β-cells. Naunyn-Schmiedeberg's Archives of Pharmacology, 361, 146–154. https://doi.org/10.1007/s002109900158

• Journal Article Type: Article
• Acceptance Date: Sep 20, 1999
• Publication Date: 2000-02
• Deposit Date: May 15, 2024
• Journal: Naunyn-Schmiedeberg's Archives of Pharmacology
• Print ISSN: 0028-1298
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 361
• Pages: 146–154
• ISBN: 00281298
• DOI: https://doi.org/10.1007/s002109900158
• Public URL: https://keele-repository.worktribe.com/output/543835