Evidence for two different imidazoline sites on pancreatic B cells and vascular bed in rat.
The relative potencies of imidazoline compounds to induce insulin secretion and vascular resistance were compared in the isolated perfused rat pancreas. On insulin secretion, only the two imidazolines, antazoline and efaroxan, induced a concentration-dependent response, antazoline being 10 times more potent than efaroxan. In contrast, idazoxan, a blocker of imidazoline I1 sites, at concentrations up to 30 microM, antagonized the insulin response to 10 microM efaroxan (IC50 approximately equal to 14 +/- 2 microM) without affecting that to 3 microM tolbutamide. On pancreatic vessels, not only antazoline and efaroxan but also idazoxan induced a concentration-dependent vasoconstriction; the rank order of agonist potency was antazoline > efaroxan > idazoxan. In addition, cimetidine, an imidazole known to bind imidazoline I1 sites, ineffective per se, partially reversed the insulin stimulatory effect of efaroxan without affecting its vasoconstrictor effect. This study demonstrates that the insulin secretory and vasoconstrictor actions of imidazolines involve different imidazoline sites in rat pancreas. The results provide evidence for an I1 type mediating insulin secretion on B cells and an I2 type mediating vasoconstriction in vessels.
Berdeu
D
D
Faculté de Médecine, Laboratoire de Pharmacologie, Institut de Biologie, Montpellier, France.
Gross
R
R
Puech
R
R
Loubatières-Mariani
M M
MM
Bertrand
G
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000865:Antazoline / Q000378:metabolism / Q000494:pharmacology; D001572:Benzofurans / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002927:Cimetidine / Q000494:pharmacology; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D012015:Reference Standards; D014044:Tolbutamide / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D004146:Dioxanes; D007093:Imidazoles; D054755:Imidazoline Receptors; D007328:Insulin; D011955:Receptors, Drug; D002927:Cimetidine; D014044:Tolbutamide; D000865:Antazoline; C062597:efaroxan; D019329:Idazoxan