ABSTRACT
The mode of inhibition of endplate currents by four esters of 1,1-dimethyl-3-oxybutyl phosphonic acid with different lipophilicities and molecule lengths were estimated by mathematical modeling based on previous electrophysiological data supplemented by several experiments with rhythmic stimulation. The aim was to discriminate between their receptor and non-receptor effects. It was shown that all esters have a two-component mechanism of depression: inhibition of the receptor open channel and allosteric modulation of the receptor-channel complex. The ratio of both functional components depends on the length and lipophilicity of the esters. Short and less lipophilic esters mostly act as open channel inhibitors and the rate of inhibition substantially depends on the rate of stimulation, i. e. probability of the receptor-channel opening. As the length of the ester radicals and their lipophilicity increased, these compounds were more active as allosteric receptor inhibitors, probably hindering the function of nAChRs from the lipid annulus.
Subject(s)
Motor Endplate/physiology , Phosphorous Acids/pharmacology , Allosteric Regulation/drug effects , Animals , Cholinergic Antagonists/pharmacology , Membrane Potentials/drug effects , Motor Endplate/drug effects , Rana pipiens , Ranidae/physiology , Receptors, Cholinergic/metabolismSubject(s)
Dust/adverse effects , Mass Screening/methods , Respiratory Hypersensitivity/epidemiology , Rhinitis, Allergic, Seasonal/epidemiology , Adolescent , Allergens , Child , Child, Preschool , Humans , Respiratory Hypersensitivity/diagnosis , Respiratory Hypersensitivity/prevention & control , Rhinitis, Allergic, Seasonal/diagnosis , Rhinitis, Allergic, Seasonal/prevention & control , Siberia , Skin Tests/methodsSubject(s)
Conjunctivitis, Allergic/etiology , Pollen , Rhinitis, Allergic, Seasonal/etiology , Child, Preschool , Humans , Infant , Male , RecurrenceSubject(s)
Desensitization, Immunologic/methods , Rhinitis, Allergic, Seasonal/immunology , Administration, Oral , Adolescent , Allergens/administration & dosage , Child , Child, Preschool , Humans , Immunity, Cellular , Immunoglobulin E/analysis , Immunoglobulin G/analysis , Infusions, Parenteral , Rhinitis, Allergic, Seasonal/therapyABSTRACT
Allergenic active fractions of ragweed, wormwood, goosefoot and sunflower pollen with a molecular weight of 37 000, 19 000, 35 000 and 14 000, respectively, were isolated by chromatography on Sephadex. All studied allergens had similar properties: affinity to Sephadex which was more pronounced to Sephadex G-75 than to G-100; absorbing components had no activity; allergenic and antigenic activities were determined only in fractions eluted in the bed volume of the column. Affinity of the allergans to Sephadex did not depend on the eluent type, but decreased in potentiation of the buffer ionic strength.
