Nezhinskaya Galina I, Vladykin Aleksandr L, Sapronov Nikolay S
Department of Neuropharmacology, Elsevier Inc.logy, Institute of Experimental Medicine, The Russian Academy of Medical Sciences, St. Petersburg 197376, Russia.
Life Sci. 2007 May 30;80(24-25):2342-6. doi: 10.1016/j.lfs.2007.04.013. Epub 2007 Apr 24.
Cholinergic drugs can modulate anaphylactic shock and change lymphocyte functions. Plasma proteins modulate effects of muscarinic antagonists during anaphylactic shock. The present investigation was carried out to study the antianaphylactic activity of methacine (antagonist at muscarinic receptors) in combination with neostigmine (anticholinesterase drug). However, it is not known whether plasma proteins-albumin, C-reactive protein (CRP) and immunoglobulin G (IgG) - modify the effects of cholinergic drugs like methacine, serotonin (5-HT) level in the lymphoid organs and quantity of antibody-forming cells (AFC) in the spleen of guinea pigs during experimental anaphylactic shock. It was shown that administration of methacine with neostigmine (40 min and 15 min prior to shock induction, accordingly) at the pathochemical stage revokes shock development. By blocking cholinesterase endogenous acetylcholine is increased and methacine blocks muscarinic receptors and therewith unwanted side effects in the airways (bronchoconstriction) and heart (bradycardia). Administration of the combination of methacine with neostigmine at the immunological stage (guinea pig sensitization) does not affect the course of anaphylactic shock. Administration of methacine with IgG at the pathochemical stage of shock significantly decreases shock intensity, while administration of methacine with CRP or albumin has no influence on the shock. Administration of IgG or CRP (not albumin) at the immunological stage of shock and albumin or IgG (not CRP) at the pathochemical stage leads to reduction of the anaphylactic reaction. Application of methacine with neostigmine or IgG (effective combinations of drugs) results in normalization of antibody response in the spleen and 5-HT level in the lymphoid organs. Administration of methacine with CRP or albumin (ineffective combinations of drugs) leads to increase of antibody response in the spleen and 5-HT level in the lymphoid organs. Administration of hexamethonium or aceclidine aggravated anaphylactic shock reaction. Thus, the combination of methacine with neostigmine can regulate the pathochemical stage of shock and the 5-HT release. At the pathochemical stage of shock IgG increases the antianaphylactic activity of methacine, but albumin and CRP abolish it.
胆碱能药物可调节过敏性休克并改变淋巴细胞功能。血浆蛋白可调节过敏性休克期间毒蕈碱拮抗剂的作用。本研究旨在探讨美他辛（毒蕈碱受体拮抗剂）与新斯的明（抗胆碱酯酶药物）联合使用的抗过敏活性。然而，尚不清楚血浆蛋白——白蛋白、C反应蛋白（CRP）和免疫球蛋白G（IgG）——在实验性过敏性休克期间是否会改变胆碱能药物如美他辛的作用、豚鼠淋巴器官中的血清素（5-HT）水平以及脾脏中抗体形成细胞（AFC）的数量。结果表明，在病理化学阶段，在诱导休克前40分钟和15分钟相应地给予美他辛和新斯的明可阻止休克的发展。通过阻断胆碱酯酶，内源性乙酰胆碱增加，美他辛阻断毒蕈碱受体，从而避免气道（支气管收缩）和心脏（心动过缓）出现不必要的副作用。在免疫阶段（豚鼠致敏）给予美他辛和新斯的明组合不影响过敏性休克的进程。在休克的病理化学阶段给予美他辛和IgG可显著降低休克强度，而给予美他辛和CRP或白蛋白对休克无影响。在休克的免疫阶段给予IgG或CRP（而非白蛋白）以及在病理化学阶段给予白蛋白或IgG（而非CRP）可减轻过敏反应。将美他辛与新斯的明或IgG联合使用（有效的药物组合）可使脾脏中的抗体反应和淋巴器官中的5-HT水平恢复正常。将美他辛与CRP或白蛋白联合使用（无效的药物组合）会导致脾脏中的抗体反应和淋巴器官中的5-HT水平升高。给予六甲铵或醋克利定会加重过敏休克反应。因此，美他辛与新斯的明的组合可调节休克的病理化学阶段和5-HT释放。在休克的病理化学阶段，IgG可增强美他辛的抗过敏活性，但白蛋白和CRP会消除这种活性。
