title: Evidence that the ability of imidazoline compounds to stimulate insulin secretion is not due to interaction with sigma receptors.
abstract: Recent studies have suggested that a variety of ion channels possess a binding site for ligands such as phencyclidine (PCP), dizocilpine and certain sigma ligands and that some imidazoline compounds can also bind to this site. We have investigated whether interaction with this binding site could account for the ability of imidazolines to stimulate insulin secretion from rat islets. Neither PCP nor dizocilpine shared the insulin secretory activity of the imidazoline efaroxan in rat islets suggesting that they do not have similar actions in the pancreatic B-cell. Further, we were able to define a new antagonist, KU14R (2(2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole), which selectively blocks the insulin secretory response to imidazolines. The results suggest that imidazolines do not stimulate insulin secretion by causing physical blockade of the K(+)-ATP channel in pancreatic B-cells and show that their effects are not reproduced by PCP or sigma receptor ligands.
authors.affiliation: Department of Biological Sciences, Keele University, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Chan
authors.forename: A L
authors.initials: AL
authors.lastname: Pallett
authors.forename: J
authors.initials: J
authors.lastname: Clews
authors.forename: C A
authors.initials: CA
authors.lastname: Ramsden
authors.forename: N G
authors.initials: NG
authors.lastname: Morgan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008024:Ligands; D010622:Phencyclidine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000187:drug effects / Q000502:physiology*
chemical_list: D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D007328:Insulin; C106086:KU 14R; D008024:Ligands; D015221:Potassium Channels; D011955:Receptors, Drug; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; C062597:efaroxan; D010622:Phencyclidine