Slf. Chan et al., EVIDENCE THAT THE ABILITY OF IMIDAZOLINE COMPOUNDS TO STIMULATE INSULIN-SECRETION IS NOT DUE TO INTERACTION WITH SIGMA-RECEPTORS, European journal of pharmacology, 323(2-3), 1997, pp. 241-244
Recent studies have suggested that a variety of ion channels possess a
binding site for ligands such as phencyclidine (PCP), dizocilpine and
certain a ligands and that some imidazoline compounds can also bind t
o this site. We have investigated whether interaction with this bindin
g site could account for the ability of imidazolines to stimulate insu
lin secretion from rat islets. Neither PCP nor dizocilpine shared the
insulin secretory activity of the imidazoline efaroxan in rat islets s
uggesting that they do not have similar actions in the pancreatic B-ce
ll. Further, we were able to define a new antagonist, KU14R (2 (2-ethy
l 2,3-dihydro-2-benzofuranyl)-2-imidazole) which selectively blocks th
e insulin secretory response to imidazolines. The results suggest that
imidazolines do not stimulate insulin secretion by causing physical b
lockade of the K+-ATP channel in pancreatic B-cells and show that thei
r effects are not reproduced by PCP or a receptor ligands.