Cholinergic modulation of anaphylactic shock: plasma proteins influence.
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.
Nezhinskaya
Galina I
GI
Department of Neuropharmacology, Elsevier Inc.logy, Institute of Experimental Medicine, The Russian Academy of Medical Sciences, St. Petersburg 197376, Russia. ginezhinskaya@mail.ru
Vladykin
Aleksandr L
AL
Sapronov
Nikolay S
NS
D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002097:C-Reactive Protein / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009388:Neostigmine / Q000494:pharmacology*; D010115:Oxyphenonium / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
D001798:Blood Proteins; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D007074:Immunoglobulin G; D018727:Muscarinic Antagonists; D012709:Serum Albumin; D012701:Serotonin; D009388:Neostigmine; D002097:C-Reactive Protein; D010115:Oxyphenonium