Cansev Mehmet, Ilcol Yesim Ozarda, Yilmaz Mustafa Sertac, Hamurtekin Emre, Ulus Ismail H
Department of Pharmacology and Clinical Pharmacology, Uludag University Medical School, Bursa, Turkey.
Eur J Pharmacol. 2008 Jul 28;589(1-3):315-22. doi: 10.1016/j.ejphar.2008.05.017. Epub 2008 May 24.
The present study was designed to test the effects of choline, cytidine-5'-diphosphocholine (CDP-choline) and phosphocholine on plasma glucagon concentrations in rats. Intraperitoneal (i.p.) injection of 200-600 micromol/kg of choline, CDP-choline or phosphocholine produced a dose-dependent increase in plasma glucagon and choline concentrations. Pretreatment with hexamethonium (15 mg/kg; i.p.), a peripherally-acting ganglionic nicotinic acetylcholine receptor antagonist, entirely blocked the increases in plasma glucagon by 600 micromol/kg of choline, CDP-choline or phosphocholine. The increases in plasma glucagon by these choline compounds was reduced significantly (P<0.01) by about 25% by pretreatment with atropine methylnitrate (2 mg/kg), a peripherally-acting muscarinic acetylcholine receptor antagonist. Blockade of central acetylcholine receptors did not alter the increase in plasma glucagon induced by i.p. choline (600 micromol/kg). While alpha(2)-adrenoceptor blockade or bilateral adrenalectomy attenuated the increase in plasma glucagon evoked by choline compounds, blockade of alpha(1)- or beta-adrenoceptors or chemical sympathectomy failed to alter this increase. Intracerebroventricular (i.c.v.) choline (1.5 micromol) administration also increased plasma glucagon; the effect was blocked by central pretreatment with a neuronal type nicotinic acetylcholine receptor antagonist, mecamylamine (50 microg; i.c.v.) or the neuronal choline uptake inhibitor, hemicholinium-3 (20 microg; i.c.v.). These data show that choline, CDP-choline or phosphocholine increases plasma glucagon concentrations by increasing peripheral nicotinic and muscarinic cholinergic neurotransmissions. Central choline also increases plasma glucagon by augmenting central nicotinic cholinergic neurotransmission by acting presynaptically. Stimulation of adrenal medullary catecholamine release and subsequent activation of alpha(2)-adrenoceptors are mainly involved in the increase in plasma glucagon induced by choline, CDP-choline or phosphocholine.
本研究旨在测试胆碱、胞苷-5'-二磷酸胆碱（CDP-胆碱）和磷酸胆碱对大鼠血浆胰高血糖素浓度的影响。腹腔注射200 - 600微摩尔/千克的胆碱、CDP-胆碱或磷酸胆碱会使血浆胰高血糖素和胆碱浓度呈剂量依赖性增加。用六甲铵（15毫克/千克；腹腔注射）进行预处理，六甲铵是一种外周作用的神经节烟碱型乙酰胆碱受体拮抗剂，可完全阻断600微摩尔/千克的胆碱、CDP-胆碱或磷酸胆碱所引起的血浆胰高血糖素增加。用硝酸甲基阿托品（2毫克/千克）进行预处理，硝酸甲基阿托品是一种外周作用的毒蕈碱型乙酰胆碱受体拮抗剂，可使这些胆碱化合物所引起的血浆胰高血糖素增加显著降低（P<0.01）约25%。阻断中枢乙酰胆碱受体不会改变腹腔注射胆碱（600微摩尔/千克）所引起的血浆胰高血糖素增加。虽然α₂-肾上腺素能受体阻断或双侧肾上腺切除术会减弱胆碱化合物所引起的血浆胰高血糖素增加，但阻断α₁-或β-肾上腺素能受体或化学交感神经切除术未能改变这种增加。脑室内注射胆碱（1.5微摩尔）也会增加血浆胰高血糖素；该效应可被用神经元型烟碱型乙酰胆碱受体拮抗剂美加明（50微克；脑室内注射）或神经元胆碱摄取抑制剂半胱氨酸-3（20微克；脑室内注射）进行中枢预处理所阻断。这些数据表明，胆碱、CDP-胆碱或磷酸胆碱通过增加外周烟碱型和毒蕈碱型胆碱能神经传递来增加血浆胰高血糖素浓度。中枢胆碱也通过突触前作用增强中枢烟碱型胆碱能神经传递来增加血浆胰高血糖素。肾上腺髓质儿茶酚胺释放的刺激以及随后α₂-肾上腺素能受体的激活主要参与了胆碱、CDP-胆碱或磷酸胆碱所引起的血浆胰高血糖素增加。
Zotero 插件