Nicotinic receptor agonist-induced salivation and its cellular mechanism in parotid acini of rats
Nicotinic receptor agonist-induced salivation and its cellular mechanism in parotid acini of rats
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DOI：
10.1016/j.autneu.2011.01.003
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发表时间：
2011-04-26
影响因子：
2.7
通讯作者：
Inenaga, Kiyotoshi
中科院分区：
文献类型：
--
作者：
Iida, Taichi;Ono, Kentaro;Inenaga, Kiyotoshi
吸烟和尼古丁促进腮腺唾液分泌，然而，其潜在机制尚不清楚。为了阐明尼古丁诱导流涎的机制并探讨尼古丁受体激动剂作为促涎剂的可能性，我们研究了尼古丁受体激动剂对大鼠体内唾液分泌和体外消化腮腺腺泡细胞内Ca（2+）浓度的影响。在麻醉大鼠中，静脉给予烟碱受体激动剂尼古丁和金雀花碱（3 μ mol/kg）可增加全唾液分泌，并伴有尼古丁升压反应，但金雀花碱无此作用。在保留自主神经末梢的消化腮腺腺泡上，用Ca（2+）显像系统，尼古丁和金雀花碱剂量依赖性地增加细胞内μ M水平的Ca（2+）浓度。这在不含神经末梢的单个腺泡细胞中未观察到。烟碱诱导的Ca（2+）反应大部分被M受体拮抗剂阻断，部分被肾上腺素能受体拮抗剂阻断。此外，相同的烟碱诱导的Ca（2+）反应被甲卡拉明阻断，甲卡拉明是一种相对选择性的α 3 β 4亚型受体的烟碱拮抗剂，但不被其他选择性拮抗剂，二氢-β-赤藓定（dihydro-beta-erythroidine）用于α 4-含受体和甲基甘草次碱（methylylycaconitine）用于α 7烟碱受体。这些结果表明，烟碱激动剂诱导的流涎是由于通过α 3 β 4烟碱受体亚型的激活从自主神经末梢释放乙酰胆碱和去甲肾上腺素。此外，考虑到血压反应和尼古丁成瘾的发展，金雀花碱可能是一个更好的治疗候选人，作为口干患者的催涎剂。皇冠版权所有（C）2011由Elsevier B. V.出版。保留所有权利。
Cigarette smoking and nicotine enhance parotid saliva secretion, however, the underlying mechanism is unclear. To address the mechanism of nicotine-induced salivation and to explore the possibility that nicotinic receptor agonists act as sialogogues, we investigated the effects of nicotinic receptor agonists on salivary secretion in vivo and on intracellular Ca(2+) concentration in digested parotid acini in vitro in rats. In urethane-anesthetized rats, intravenous administration of nicotinic receptor agonists, nicotine and cytisine, at 3 mu mol/kg increased whole saliva output accompanied by a pressor response with nicotine, but not with cytisine. Using Ca(2+)-imaging system on digested parotid acini in which autonomic nerve terminals were kept intact, nicotine and cytisine dose-dependently increased intracellular Ca(2+) concentration at mu M level. This was not observed in single acinar cells containing no nerve terminal. The nicotine-induced Ca(2+) response was largely blocked by a muscarinic receptor antagonist and partly blocked by an adrenergic receptor antagonist. Furthermore, the same nicotine-induced Ca(2+) response was blocked by mecamylamine, a relatively selective nicotinic antagonist for alpha 3 beta 4 subtype receptor, but not by other selective antagonists, dihydro-beta-erythroidine for alpha 4-containing receptor and methyllycaconitine for alpha 7 nicotinic receptors. These results suggest that nicotinic agonists-induced salivation is due to a release of acetylcholine and noradrenaline from autonomic nerve terminals through activation of alpha 3 beta 4 nicotinic receptor subtype. In addition, considering the blood pressure response and development of addiction with nicotine, cytisine may be a better therapeutic candidate to serve as a sialogogue for xerostomia patients. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.