Mayer Gaëll, Taberner Peter V
Department of Pharmacology, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Eur J Pharmacol. 2002 Nov 1;454(1):95-102. doi: 10.1016/s0014-2999(02)02473-1.
The putative imidazoline I(3) receptor antagonist 2-(2-ethyl-2,3-dihydrobenzo[b]furan-2-yl)-1H-imidazole (KU14R) has been shown to block the effects of the atypical I(3) agonist efaroxan at the level of the ATP-sensitive K(+) (K(ATP)) channel in isolated pancreatic islet beta cells, but its effects in vivo are not known. We have therefore investigated the effects of KU14R on blood glucose and insulin level in vivo. When KU14R was administered before or after a hypoglycaemic dose of efaroxan, the fall in blood glucose was at least additive. When the antihyperglycaemic imidazoline ligand S22068 was administered after a dose of KU14R, it did not alter the hypoglycaemic response. In the mouse isolated vas deferens preparation, neither rauwolscine (at concentrations which competitively antagonised the inhibitory response to 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK14304)) nor KU14R affected inhibition produced by S22068. At 10(-4) M, KU14R had weak alpha(2)-adrenoceptor antagonist activity. We conclude that KU14R does not act as an antagonist of either efaroxan or S22068 at an imidazoline site in vivo.
公认的咪唑啉I(3)受体拮抗剂2-(2-乙基-2,3-二氢苯并[b]呋喃-2-基)-1H-咪唑(KU14R)已被证明可在分离的胰岛β细胞中，在ATP敏感性钾(K(ATP))通道水平阻断非典型I(3)激动剂依酚氯铵的作用，但其体内作用尚不清楚。因此，我们研究了KU14R对体内血糖和胰岛素水平的影响。在给予低血糖剂量的依酚氯铵之前或之后给予KU14R，血糖下降至少是相加的。在给予一剂KU14R后给予抗高血糖咪唑啉配体S22068，它并未改变低血糖反应。在小鼠离体输精管制备中，无论是萝芙木碱(在竞争性拮抗对5-溴-6-(2-咪唑啉-2-基氨基)-喹喔啉(UK14304)的抑制反应的浓度下)还是KU14R都不影响S22068产生的抑制作用。在10(-4)M时，KU14R具有较弱的α(2)-肾上腺素能受体拮抗剂活性。我们得出结论，在体内，KU14R在咪唑啉位点既不充当依酚氯铵也不充当S22068的拮抗剂。
