咪唑克生及其2-甲氧基衍生物RX 821002 [纠正为RX 821001] 对兔α2-肾上腺素能受体和非肾上腺素能受体咪唑克生结合位点的7天治疗效果。

Effect of a 7-day treatment with idazoxan and its 2-methoxy derivative RX 821002 [correction of RX 821001] on alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites in rabbits.

作者信息

Portillo M, Reverte M, Langin D, Senard J M, Tran M A, Berlan M, Montastruc J L

机构信息

Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.

出版信息

Br J Pharmacol. 1991 Sep;104(1):190-4. doi: 10.1111/j.1476-5381.1991.tb12406.x.

DOI:10.1111/j.1476-5381.1991.tb12406.x

PMID:1686202

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908292/

Abstract

The present study investigates the influence of a 7-day treatment with 2 mg kg-1, s.c., twice daily of RX 821002 (an alpha 2-adrenoceptor antagonist which binds only to alpha 2-adrenoceptors) or idazoxan (alpha 2-antagonist which binds to alpha 2-adrenoceptors and also to non-adrenoceptor idazoxan binding sites: NAIBS) on alpha 2-adrenoceptor (labelled with [3H]-RX 821002) and NAIBS (labelled with [3H]-idazoxan) number in three tissues (adipocytes, colocytes and platelets) in the rabbit. 2. Acute administration of RX 821002 or idazoxan increased plasma non-esterified fatty acids (NEFA) and catecholamine levels with no change in plasma glucose levels. 3. The 7-day treatment with RX 821002 or idazoxan failed to influence food intake, total body weight or perirenal adipose tissue weight. 4. RX 821002 and idazoxan increased the number of [3H]-RX 821002 binding sites in adipose tissue with no change in colocytes or platelets. 5. RX 821002 and idazoxan failed to modify [3H]-idazoxan binding sites on adipocytes and colocytes. No significant [3H]-idazoxan binding was detected on rabbit platelets. 6. The results show that a 7-day treatment with alpha 2-antagonists induces an up-regulation in adipocyte alpha 2-adrenoceptors. In contrast, this phenomenon does not involve all the tissues since colocytes and platelets escape the effects of alpha 2-antagonists. The data suggest a differential regulation of alpha 2-adrenoceptors according to their location. 7. The fact that NAIBS did not vary suggests that alpha 2-adrenoceptors and NAIBS are two different entities. Finally, since RX 821002 and idazoxan exert similar effects after either acute or chronic treatment, it is suggested that NAIBS are not involved in the control of catecholamine release or in NEFA or glucose metabolism.

摘要

本研究调查了用2毫克/千克体重、皮下注射、每日两次的RX 821002（一种仅与α2 - 肾上腺素能受体结合的α2 - 肾上腺素能受体拮抗剂）或咪唑克生（一种与α2 - 肾上腺素能受体以及非肾上腺素能咪唑克生结合位点：NAIBS结合的α2 - 拮抗剂）进行为期7天的治疗对兔三种组织（脂肪细胞、结肠细胞和血小板）中α2 - 肾上腺素能受体（用[3H] - RX 821002标记）和NAIBS（用[3H] - 咪唑克生标记）数量的影响。2. 急性给予RX 821002或咪唑克生可使血浆非酯化脂肪酸（NEFA）和儿茶酚胺水平升高，而血浆葡萄糖水平无变化。3. 用RX 821002或咪唑克生进行为期7天的治疗未能影响食物摄入量、总体重或肾周脂肪组织重量。4. RX 821002和咪唑克生增加了脂肪组织中[3H] - RX 821002结合位点的数量，而结肠细胞或血小板中的数量无变化。5. RX 821002和咪唑克生未能改变脂肪细胞和结肠细胞上的[3H] - 咪唑克生结合位点。在兔血小板上未检测到明显的[3H] - 咪唑克生结合。6. 结果表明，用α2 - 拮抗剂进行为期7天的治疗可诱导脂肪细胞α2 - 肾上腺素能受体上调。相比之下，这种现象并不涉及所有组织，因为结肠细胞和血小板不受α2 - 拮抗剂的影响。数据表明α2 - 肾上腺素能受体根据其位置存在差异调节。7. NAIBS没有变化这一事实表明α2 - 肾上腺素能受体和NAIBS是两个不同的实体。最后，由于RX 821002和咪唑克生在急性或慢性治疗后产生相似的效果，提示NAIBS不参与儿茶酚胺释放的控制或NEFA或葡萄糖代谢。