Bugajski A J, Zurowski D, Thor P, Gadek-Michalska A
Department of Pathophysiology Medical College, Jagiellonian University, Cracow, Poland.
J Physiol Pharmacol. 2007 Jun;58(2):335-47.
In the present study, we examined whether the vagus nerve is involved in mediating the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic muscarinic and nicotinic agonists, carbachol and nicotine. The site of HPA axis muscarinic stimulation was determined using peripheral (i.p.) and intracerebroventricular (i.c.v.) administration of carbachol, atropine sulphate (AtrS) and atropine hydrobromide (AtrBr). The i.p. carbachol-(0.5 mg/kg)-induced corticosterone response was significantly reduced by i.p. pretreatment with AtrBr (0.1 mg/kg), but was not diminished by i.c.v. AtrS (0.1 mug). The increase in corticosterone secretion induced by i.c.v. carbachol (2 microg) was totally abolished by i.c.v. pretreatment with AtrS (0.1 microg) but was not altered by i.p. AtrBr. Subdiaphragmatic vagotomy performed 2 weeks earlier substantially decreased the i.p. carbachol (0.2 mg/kg)-induced ACTH response and markedly augmented ACTH and corticosterone response to a higher dose of carbachol (0.5 mg/kg) in comparison with the responses in sham operated rats. Vagotomy abolished the stimulatory effect of i.p. nicotine in a low dose (1 mg/kg) on ACTH and corticosterone secretion; the ACTH response to higher dose (2.5 mg/kg) was considerably reduced, while corticosterone response remained unaffected. These results suggest that carbachol given i.c.v. evokes considerable corticosterone response by stimulation of central cholinergic muscarinic receptors. A major part of the i.p. carbachol-induced corticosterone secretion results from peripheral cholinergic muscarinic receptor stimulation. Subdiaphragmatic vagotomy moderately intensified the carbachol-induced ACTH and corticosterone secretion. Vagotomy significantly reduced the nicotine-induced ACTH secretion, possibly by the involvement of vagal afferents. The nicotine-induced corticosterone secretion is not exclusively regulated by circulating ACTH but by various intra-adrenal regulatory components.
在本研究中，我们检测了迷走神经是否参与介导胆碱能毒蕈碱和烟碱激动剂（卡巴胆碱和尼古丁）对下丘脑-垂体-肾上腺（HPA）轴的刺激作用。使用卡巴胆碱、硫酸阿托品（AtrS）和氢溴酸阿托品（AtrBr）的外周（腹腔注射）和脑室内（脑室内注射）给药来确定HPA轴毒蕈碱刺激的部位。腹腔注射AtrBr（0.1mg/kg）预处理可显著降低腹腔注射卡巴胆碱（0.5mg/kg）诱导的皮质酮反应，但脑室内注射AtrS（0.1μg）则不会使其减弱。脑室内注射卡巴胆碱（2μg）诱导的皮质酮分泌增加被脑室内注射AtrS（0.1μg）预处理完全消除，但腹腔注射AtrBr则不会改变。与假手术大鼠相比，提前2周进行膈下迷走神经切断术可显著降低腹腔注射卡巴胆碱（0.2mg/kg）诱导的促肾上腺皮质激素（ACTH）反应，并显著增强对更高剂量卡巴胆碱（0.5mg/kg）的ACTH和皮质酮反应。迷走神经切断术消除了低剂量（1mg/kg）腹腔注射尼古丁对ACTH和皮质酮分泌的刺激作用；对更高剂量（2.5mg/kg）的ACTH反应显著降低，而皮质酮反应仍未受影响。这些结果表明，脑室内注射卡巴胆碱通过刺激中枢胆碱能毒蕈碱受体引起显著的皮质酮反应。腹腔注射卡巴胆碱诱导的皮质酮分泌主要源于外周胆碱能毒蕈碱受体刺激。膈下迷走神经切断术适度增强了卡巴胆碱诱导的ACTH和皮质酮分泌。迷走神经切断术显著降低了尼古丁诱导的ACTH分泌，可能是通过迷走神经传入参与。尼古丁诱导的皮质酮分泌并非仅由循环ACTH调节，而是由多种肾上腺内调节成分调节。
