EVIDENCE FOR 2 DIFFERENT IMIDAZOLINE SITES ON PANCREATIC B-CELLS AND VASCULAR BED IN RAT

The relative potencies of imidazoline compounds to induce insulin secr etion and vascular resistance were compared in the isolated perfused r at pancreas. On insulin secretion, only the two imidazolines, antazoli ne and efaroxan, induced a concentration-dependent response, antazolin e being 10 times more potent than efaroxan. In contrast, idazoxan, a b locker of imidazoline I-1 sites, at concentrations up to 30 mu M, anta gonized the insulin response to 10 mu M efaroxan (IC50 congruent to 14 +/- 2 mu M) without affecting that to 3 mu M tolbutamide. On pancreat ic 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 I-1 sites, ineffective per se , partially reversed the insulin stimulatory effect of efaroxan withou t affecting its vasoconstrictor effect. This study demonstrates that t he insulin secretory and vasoconstrictor actions of imidazolines invol ve different imidazoline sites in rat pancreas. The results provide ev idence for an I-1 type mediating insulin secretion on B cells and an I -1 type mediating vasoconstriction in vessels.