Selected serotonergic compounds, through a CNS-site of action, appear to be able to release sulfonylurea-like peptides from the pituitary gland. The therapeutic significance of sulfonylurea compounds, like glibenclamide and tolbutamide, in the treatment of type II diabetes for regulating plasma glucose levels has been recognized for decades without a full appreciation of the mechanism of action of these compounds, nature of the receptor, or the demonstration of the existence of endogenous ligands. After extensive isolation and characterization of sulfonylurea- like activity in the CNS and pituitary gland, several peptide fractions have emerged from the pituitary gland which: (1) enhance insulin secretion, (2) inhibit sulfonylurea drug binding to sulfonylurea receptors, and (3) appear to mimic the electrophysiological membrane changes observed with sulfonylurea drugs. A novel peptide and a known peptide with a novel function have emerged from these studies. It is envisioned that there exists a family of novel endogenous peptides which modulate sulfonylurea receptors.We have demonstrated that a member of the non-histone nuclear protein group mimics many of the actions of the sulfonylurea compounds and this compound appears to be an intracellular regulator of the sulfonylurea receptor. Only data analysis and manuscript work were performed on this project.
