title: Pertussis toxin converts hyperpolarizations caused by alpha(2)-adrenoceptor agonists containing an imidazoline moiety into depolarizations in MIN 6 cells.
abstract: Several alpha(2)-adrenoceptor agonists containing an imidazoline moiety inhibit insulin secretion when applied to beta cells. In the present study we investigated such imidazolines in regard to membrane potential effects in MIN 6 cells. We confirmed the inhibition of insulin release as reported in previous studies and showed an additional hyperpolarizing activity of the imidazolines using bisoxonol for membrane potential measurements. Pertussis toxin pre-incubation of MIN 6 cells converted the inhibitory imidazoline activity with regard to insulin release into a stimulatory effect. In addition, the marked hyperpolarization caused by the alpha-adrenoceptor agonists containing an imidazoline moiety was converted into a depolarizing effect after pertussis toxin pre-incubation. Adrenaline, an alpha-adrenoceptor agonist lacking an imidazoline moiety, also inhibited insulin release and hyperpolarized MIN 6 cells. Pertussis toxin pre-incubation led only to a loss of the inhibitory adrenaline effect and of the hyperpolarization but not to the stimulatory effects observed with the imidazolines. Thus a stimulatory effect of alpha-adrenoceptor agonists containing an imidazoline moiety was demasked by PTX in this study. It remains to be clarified to which extent a blockade of K(ATP) channels is responsible for this effect.
authors.affiliation: Lilly Research Laboratories, Department of Pharmacology, Essener Strasse 93, 22419 Hamburg, Germany.
authors.forename: Mathis
authors.initials: M
authors.lastname: Scheltdorf
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Mest
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D003000:Clonidine / Q000737:chemistry / Q000494:pharmacology; D004837:Epinephrine / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010109:Oxymetazoline / Q000737:chemistry / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D007328:Insulin; D018341:Receptors, Adrenergic, alpha-2; D010109:Oxymetazoline; C043482:moxonidine; D037342:Pertussis Toxin; D003000:Clonidine; D004837:Epinephrine