[Non-neuronal effects of muscarinic antagonists in the prophylaxis of stress].
We have studied the stress-limiting role of the immune reaction initiated by cholinergic antagonists and the influence of these drugs on the dynamics of antibody formation in the spleen and the blood serum corticosterone level. The protective effect of immune reaction initiated by methacine (muscarinic receptor antagonist) or hexamethonium (nicotinic receptor antagonist) in prevention of stress gastric ulcer in rats (induced by water immersion stress, WIS) was estimated upon administration of the drugs for 5 days (local response) or 14 days (systemic response) prior to WIS. The pharmacological effects of drugs were estimated upon their administration 30 minutes prior to WIS. It is shown that, if cholinergic antagonists affect the systemic immune response the induction of WIS at this level of immune reaction leads to the effective prevention of stress gastric ulcer. The administration of methacine (but not hexamethonium) 14 days prior to WIS effectively reduces gastric lesions up to 1.0 +/- 0.1 arbitrary units in comparison to 3.6 + 0.2 arbitrary units in the control group. Under effective prophylaxis, the number of antibody-forming cells (AFC/10(6) of splenocytes) and corticosterone concentration are close to their basal level, while under stress conditions, these parameters significantly increase up to 870 +/- 21 and 350 +/- 4 vs. 100 +/- 17 and 107 +/- 6 in the control group, accordingly. It is established that both methacine and hexamethonium remain immunologically active for 28 days and more: the maximum amount of AFC upon administration of hexamethonium and methacine was on the 5th day and 14th day, respectively. Thus, determination of the drug influence on the systemic immune response allows one to predict the non-neuronal effects of cholinergic antagonists and, in this way, to affect the pathogenesis of stress gastric ulcer. Estimation of the AFC response and corticosterone level after WIS shows the efficacy ofprophylaxis of the gastric stress lesion.
Nezhinskaia
G I
GI
Vladykin
A L
AL
Sapronov
N S
NS
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000187:drug effects; D001561:Benzilates / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D005753:Gastric Mucosa / Q000473:pathology; D018738:Hexamethonium / Q000494:pharmacology; D007101:Immersion; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013276:Stomach Ulcer / Q000209:etiology / Q000473:pathology; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology / Q000517:prevention & control*
D001561:Benzilates; D018727:Muscarinic Antagonists; C053908:metacine; D018738:Hexamethonium; D002794:Choline; D003345:Corticosterone