Berdeu D, Gross R, Puech R, Loubatières-Mariani M M, Bertrand G
Faculté de Médecine, Laboratoire de Pharmacologie, Institut de Biologie, Montpellier, France.
Eur J Pharmacol. 1995 Feb 24;275(1):91-8. doi: 10.1016/0014-2999(94)00757-x.
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.
在离体灌注大鼠胰腺中比较了咪唑啉化合物诱导胰岛素分泌和血管阻力的相对效能。关于胰岛素分泌，只有两种咪唑啉，即安他唑啉和依酚氯铵，能诱导浓度依赖性反应，安他唑啉的效能比依酚氯铵高10倍。相比之下，咪唑啉I1位点阻滞剂伊达唑胺在浓度高达30μM时，可拮抗对10μM依酚氯铵的胰岛素反应（IC50约等于14±2μM），而不影响对3μM甲苯磺丁脲的反应。在胰腺血管上，不仅安他唑啉和依酚氯铵，而且伊达唑胺也能诱导浓度依赖性血管收缩；激动剂效能的顺序为安他唑啉>依酚氯铵>伊达唑胺。此外，已知能结合咪唑啉I1位点的咪唑类药物西咪替丁本身无效，但能部分逆转依酚氯铵对胰岛素的刺激作用，而不影响其血管收缩作用。本研究表明，咪唑啉的胰岛素分泌和血管收缩作用涉及大鼠胰腺中不同的咪唑啉位点。结果为B细胞上介导胰岛素分泌的I1型和血管中介导血管收缩的I2型提供了证据。
