ABSTRACT
Using electrophysiology, the effect of nicotinic acetylcholine receptor (nAChR) ligands on acetylcholine-induced depolarization in the neurons of Helix lucorum snail was studied. It was found that the α-conotoxin PnIA [R9, L10], a selective antagonist of α7 nAChR, and α-cobratoxin (antagonist of α7 and muscle-type nAChR) suppressed neuronal depolarization. Fluorescence microscopy showed staining of the neurons with fluorescently labeled α-bungarotoxin; this staining was reduced by pretreatment with α-cobratoxin. Induced depolarization was also suppressed by α-conotoxin RgIA, a selective inhibitor of α9 nAChR. In contrast to Lymnaea stagnalis nAChR, which are weakly sensitive to neurotoxin II and α-conotoxin GI, antagonists of muscle-type nAChR, H. lucorum receptors were most effectively inhibited by these antagonists. The results obtained, as well as the previously found sensitivity of the receptors studied in this work to muscarinic receptor ligands, indicate an unusual atypical pharmacological profile of H. lucorum nAChR.
Subject(s)
Neurons/metabolism , Receptors, Cholinergic/metabolism , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Acetylcholine/metabolism , Animals , Binding Sites , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bungarotoxins/metabolism , Helix, Snails , Ligands , Microscopy, Confocal , Microscopy, Fluorescence , Neurotoxins/metabolism , Pyridines/pharmacology , Signal TransductionABSTRACT
Comparison of the cognition-stimulating effects of Dimebon in a wide dose range revealed a non-monotonic and nontrivial wave-like dose-dependence of its activity. Positive results were obtained at low (0.02-0.05 mg/kg) or high (5-10 mg/kg) doses of Dimebon, while intermediate doses were ineffective. This type of the dose dependence of the pharmacological effect can indicate that the substance has several targets. This fact should be taken into consideration when selecting the doses and concentrations of the substance and its analogues for further studies, and for planning treatment schemes and administration doses in clinical studies.
Subject(s)
Central Nervous System Stimulants/pharmacology , Cognition/drug effects , Indoles/pharmacology , Alzheimer Disease/chemically induced , Alzheimer Disease/pathology , Alzheimer Disease/psychology , Animals , Aziridines , Biological Clocks/drug effects , Choline/analogs & derivatives , Cognition/physiology , Disease Models, Animal , Dose-Response Relationship, Drug , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Pattern Recognition, Physiological/drug effects , Rats , Rats, WistarABSTRACT
We studied the effect of flavonoid taxifolin (dihydriquercetin) on the structure and thermal stability of collagen I fibrils. Taxifolin accelerated fibril formation with reconstruction of periodical cross-striation characteristic of these fibrils. Differential scanning calorimetry showed elevation of melting temperature of collagen fibrils formed in neutral or weakly alkaline media, but not of individual tropocollagen molecules in acid medium. Taxifolin capacity to stimulate fibril formation and promote stabilization of fibrillar forms of collagen can be used in medicine.
