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β₁受体可能参与多种致吐原引起的大鼠唾液淀粉酶活性增加。

Possible involvement of β₁ receptors in various emetogen-induced increases in salivary amylase activity in rats.

机构信息

Development Research Center, Takeda Pharmaceutical Company, Ltd., Osaka, Japan.

出版信息

J Pharmacol Sci. 2011;115(1):69-74. doi: 10.1254/jphs.10265fp. Epub 2010 Dec 14.

Abstract

We investigated the inhibitory effects of β₁- or β₂-adrenoceptor (AR) antagonists on salivary amylase secretion produced by various emetic agents, such as cisplatin, apomorphine, and lithium chloride (LiCl), or the non-emetic agent β(½)-AR agonist isoprenaline in rats. We also determined the inhibitory effect of metoclopramide, a dopamine D₂-receptor antagonist, on increases in the salivary amylase activity induced by apomorphine or granisetron, a 5-HT(3)-receptor antagonist, on LiCl-induced increased salivary amylase activity. Isoprenaline (0.01 mg/kg, s.c.) produced an increase in salivary amylase and the increase was inhibited by the β(½)-AR antagonist propranolol (5 mg/kg, s.c.) and β₁-AR antagonist atenolol (2 mg/kg, s.c.) but not by the β₂-AR antagonist butoxamine (8 mg/kg, s.c.). The increased amylase activity induced by cisplatin (15 mg/kg, i.v.), apomorphine (3 mg/kg, s.c.), or LiCl (120 mg/kg, i.p.) was inhibited significantly by atenolol (2 mg/kg, s.c.) but not by butoxamine (8 mg/kg, s.c.). In addition, increases in amylase activities induced by apomorphine and LiCl were inhibited significantly by metoclopramide (10 mg/kg, i.v.) and granisetron (3 mg/kg, i.v.), respectively. These results suggest that salivary amylase secretion induced by various emetogens is involved in β₁-adrenoceptor activity and that salivary amylase activity is useful to detect emetogens with no direct β₁-AR activation in rats, a species that does not exhibit vomiting.

摘要

我们研究了β₁-或β₂-肾上腺素受体(AR)拮抗剂对顺铂、阿扑吗啡和氯化锂(LiCl)等催吐剂或非催吐剂β(½)-AR 激动剂异丙肾上腺素引起的大鼠唾液淀粉酶分泌的抑制作用。我们还测定了多巴胺 D₂-受体拮抗剂甲氧氯普胺对阿扑吗啡或 5-HT₃-受体拮抗剂格兰司琼引起的唾液淀粉酶活性增加的抑制作用,以及 LiCl 引起的唾液淀粉酶活性增加。异丙肾上腺素(0.01 mg/kg,皮下注射)可增加唾液淀粉酶,该增加被β(½)-AR 拮抗剂普萘洛尔(5 mg/kg,皮下注射)和β₁-AR 拮抗剂阿替洛尔(2 mg/kg,皮下注射)抑制,但不受β₂-AR 拮抗剂丁氧胺(8 mg/kg,皮下注射)抑制。顺铂(15 mg/kg,静脉注射)、阿扑吗啡(3 mg/kg,皮下注射)或 LiCl(120 mg/kg,腹腔注射)引起的淀粉酶活性增加被阿替洛尔(2 mg/kg,皮下注射)显著抑制,但不受丁氧胺(8 mg/kg,皮下注射)抑制。此外,阿扑吗啡和 LiCl 引起的淀粉酶活性增加分别被甲氧氯普胺(10 mg/kg,静脉注射)和格兰司琼(3 mg/kg,静脉注射)显著抑制。这些结果表明,各种催吐剂引起的唾液淀粉酶分泌与β₁-AR 活性有关,并且唾液淀粉酶活性可用于检测在不表现呕吐的大鼠中没有直接β₁-AR 激活的催吐剂。

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