EVIDENCE FOR 2 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 I-1 sites, at concentrations up to 30 mu M, antagonized the insulin response to 10 mu M efaroxan (IC50 congruent to 14 +/- 2 mu M) without affecting that to 3 mu M 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 I-1 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 I-1 type mediating insulin secretion on B cells and an I-1 type mediating vasoconstriction in vessels.