Department of Biosciences, Kyushu Dental College, 2-6-1 Manazuru, Kokurakitaku, Kitakyushu, Fukuoka 803-8580, Japan.
Auton Neurosci. 2011 Apr 26;161(1-2):81-6. doi: 10.1016/j.autneu.2011.01.003.
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 Ca²+ concentration in digested parotid acini in vitro in rats. In urethane-anesthetized rats, intravenous administration of nicotinic receptor agonists, nicotine and cytisine, at 3 μmol/kg increased whole saliva output accompanied by a pressor response with nicotine, but not with cytisine. Using Ca²+-imaging system on digested parotid acini in which autonomic nerve terminals were kept intact, nicotine and cytisine dose-dependently increased intracellular Ca²+ concentration at μM level. This was not observed in single acinar cells containing no nerve terminal. The nicotine-induced Ca²+ response was largely blocked by a muscarinic receptor antagonist and partly blocked by an adrenergic receptor antagonist. Furthermore, the same nicotine-induced Ca²+ response was blocked by mecamylamine, a relatively selective nicotinic antagonist for α3β4 subtype receptor, but not by other selective antagonists, dihydro-β-erythroidine for α4-containing receptor and methyllycaconitine for α7 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 α3β4 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.
吸烟和尼古丁会促进腮腺分泌唾液，但其中的机制尚不清楚。为了研究尼古丁诱导唾液分泌的机制，以及探索烟碱受体激动剂是否具有唾液分泌作用，我们研究了烟碱受体激动剂对大鼠体内唾液分泌的影响，以及对体外消化腮腺中细胞内钙离子浓度的影响。在乌拉坦麻醉的大鼠中，静脉给予 3μmol/kg 的烟碱受体激动剂尼古丁和烟碱甲硫氨酸，可增加全唾液分泌，并伴有血压升高，而烟碱甲硫氨酸则没有。在保持自主神经末梢完整的消化腮腺中，使用钙离子成像系统，尼古丁和烟碱甲硫氨酸在微摩尔水平上呈剂量依赖性地增加细胞内钙离子浓度。在不含神经末梢的单个腺泡细胞中未观察到这种现象。尼古丁诱导的 Ca²+反应被毒蕈碱受体拮抗剂和肾上腺素能受体拮抗剂部分阻断。此外，同样的尼古丁诱导的 Ca²+反应被烟碱受体α3β4 亚基选择性拮抗剂美加明阻断，但不被其他选择性拮抗剂二氢-β-erythroidine（α4 受体）和甲基lycaconitine（α7 烟碱受体）阻断。这些结果表明，烟碱激动剂诱导的唾液分泌是由于自主神经末梢释放乙酰胆碱和去甲肾上腺素，通过激活α3β4 烟碱受体亚型。此外，考虑到尼古丁引起的血压反应和成瘾性，烟碱甲硫氨酸可能是治疗口干症患者的更好的治疗候选药物。
