title: Effects of the imidazoline ligands efaroxan and KU14R on blood glucose homeostasis in the mouse.
abstract: The putative imidazoline I(3) receptor antagonist 2-(2-ethyl-2,3-dihydrobenzo[b]furan-2-yl)-1H-imidazole (KU14R) has been shown to block the effects of the atypical I(3) agonist efaroxan at the level of the ATP-sensitive K(+) (K(ATP)) channel in isolated pancreatic islet beta cells, but its effects in vivo are not known. We have therefore investigated the effects of KU14R on blood glucose and insulin level in vivo. When KU14R was administered before or after a hypoglycaemic dose of efaroxan, the fall in blood glucose was at least additive. When the antihyperglycaemic imidazoline ligand S22068 was administered after a dose of KU14R, it did not alter the hypoglycaemic response. In the mouse isolated vas deferens preparation, neither rauwolscine (at concentrations which competitively antagonised the inhibitory response to 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK14304)) nor KU14R affected inhibition produced by S22068. At 10(-4) M, KU14R had weak alpha(2)-adrenoceptor antagonist activity. We conclude that KU14R does not act as an antagonist of either efaroxan or S22068 at an imidazoline site in vivo.
authors.affiliation: Department of Pharmacology, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
authors.forename: Gaëll
authors.initials: G
authors.lastname: Mayer
authors.forename: Peter V
authors.initials: PV
authors.lastname: Taberner
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D006706:Homeostasis; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008024:Ligands; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D007328:Insulin; C106086:KU 14R; D008024:Ligands; D010879:Piperazines; D011810:Quinoxalines; D011955:Receptors, Drug; C116061:S 22068; D000068438:Brimonidine Tartrate; C062597:efaroxan