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β肾上腺素能受体的体温调节作用:选择性激动剂的作用以及拮抗剂与异丙肾上腺素和BRL-35135在寒冷环境中的相互作用

Thermoregulatory effects of beta adrenoceptors: effects of selective agonists and the interaction of antagonists with isoproterenol and BRL-35135 in the cold.

作者信息

Carlisle H J, Stock M J

机构信息

Department of Psychology, University of California, Santa Barbara.

出版信息

J Pharmacol Exp Ther. 1993 Sep;266(3):1446-53.

PMID:8103795
Abstract

Dose-dependent effects of the selective beta 1 adrenergic antagonist atenolol and the beta 2 antagonist erythro-dl-1-(7-methylinden-4-yloxy)-3-isopropylamino-2-ol were tested on the thermoregulatory responses elicited by half-maximal thermogenic doses of the nonselective beta agonist isoproterenol (ISO) in a cold environment. ISO alone increased operant responding for exogenous heat but decreased body temperature and increased net heat loss. These effects of ISO were blocked by erythro-dl-1-(7-methylinden-4-yloxy)3-isopropylamino-2-ol in a dose-dependent manner, whereas atenolol at the highest dose tested (2 mg/kg) exacerbated the effects of ISO. The beta 3 agonist, (R*,R*-(+/-)-methyl 4-[2-[2-hydroxy-2-(3-chlorophenyl)ethylamino]propylphenoxyacetate hydrobromide, reduced operant responding for heat and net heat loss in the cold; these effects were sustained in the presence of both beta 1 and beta 2 antagonists. The beta 2 adrenoceptor agonist, fenoterol, produced a dose-dependent increase in operant behavior but colonic temperature fell and thermal balance reflected the characteristic effects of a thermolytic agent. The beta 1 agonist, prenalterol, had no apparent effect on thermoregulatory behavior, colonic temperature or thermal balance but it blocked the thermolytic effects of fenoterol when both agonists were coadministered. Fenoterol had no significant effect on metabolic rate or colonic temperature when tested in a warm ambient temperature of 23 degrees C but it decreased colonic temperature without a significant effect on metabolic rate at an ambient temperature of 5 degrees C, suggesting an effect on heat loss mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在寒冷环境中,测试了选择性β1肾上腺素能拮抗剂阿替洛尔和β2拮抗剂erythro-dl-1-(7-甲基茚-4-基氧基)-3-异丙基氨基-2-醇的剂量依赖性效应,这些效应作用于由非选择性β激动剂异丙肾上腺素(ISO)的半最大产热剂量引发的体温调节反应。单独使用ISO会增加对外源热的操作性反应,但会降低体温并增加净热损失。erythro-dl-1-(7-甲基茚-4-基氧基)3-异丙基氨基-2-醇以剂量依赖性方式阻断了ISO的这些效应,而在测试的最高剂量(2mg/kg)下,阿替洛尔会加剧ISO的效应。β3激动剂(R*,R*-(+/-)-甲基4-[2-[2-羟基-2-(3-氯苯基)乙基氨基]丙基苯氧基乙酸氢溴酸盐可降低寒冷环境中对热的操作性反应和净热损失;在同时存在β1和β2拮抗剂的情况下,这些效应依然存在。β2肾上腺素能受体激动剂非诺特罗会使操作性行为呈剂量依赖性增加,但结肠温度下降,热平衡反映出一种热解剂的特征性效应。β1激动剂普瑞特罗对体温调节行为、结肠温度或热平衡没有明显影响,但当两种激动剂同时给药时,它会阻断非诺特罗的热解效应。在23摄氏度的温暖环境温度下测试时,非诺特罗对代谢率或结肠温度没有显著影响,但在5摄氏度的环境温度下,它会降低结肠温度,而对代谢率没有显著影响,这表明其对热损失机制有影响。(摘要截取自250字)

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