[The role of cytochrome p450 in metabolism of S-ethynylthiophosphates]. / Rol' tsitokhroma p450 v metabolizme S-étiniltiophosfatov.

We studied interaction between S-ethynyl ethers of phosphorus acids with cytochrome P-450 from rat liver and housefly abdomen. High thionic effect, i.e., considerable selectivity for the studied compounds in homoiotherms and arthropods, proved to the related to the triple bond in these compounds. Apparently, cytochrome P-450 participates in S-ethynylthiophosphates metabolism and breaks the P-S bond. This gives rise to "self-destroying" metabolites, namely, alkylthioketenes, which decelerate deactivation reactions through destruction of the corresponding isoform of cytochrome P-450 in the microsomal fraction in both homoiotherms and insects. However, the activation reaction goes much faster in insects than in homoiotherms.

[Mechanism of the "acetylene effect" during interaction of organophosphorus compounds with cholinesterases]. / O mekhanizme "atsetilenovogo éffecta" pri vzaimodeistvii fosfororganicheskikh soedinenii s kholinésterazami.

Here we present data on the anticholinesterase activity of 58 synthesized ethers of phosphorus thioacids with an acetylene bond in the thioether group. Anticholinesterase activity of the compounds, with acetylene group in beta and especially alpha position, in the thioether radical is many times that of their saturated analogs. Reaction between the enzymes and acetylene organophosphorous inhibitors, as well as their saturated analogs, results in phosphorylated enzyme. The triple bond plays a significant role in the acceleration of cholinesterases phosphorylation. Antienzyme activity of acetylene organophosphorous inhibitors is discussed.

[The mechanism of anticholinesterase action of acetylene organophosphorus inhibitors]. / O mekhanizme antikholinésteraznogo deistviia atsetilenovykh fosforororganicheskikh ingibitorov.

Introduction of the triple bond in the leaving group of the organophosphorus inhibitor molecule gives a sharp raise of the inhibitor activity but does not change principal characteristics of the cholinesterase inhibition mechanism. The reactivation experiments suggest that inactivation of cholinesterases by these compounds occurs due to phosphorylating of the serine hydroxyl by the corresponding phosphoric acid. A close similarity was shown between acetylenic and saturated organophosphorus inhibitors in altering ka upon change of pH and tetraalkylammonium ions action. It is demonstrated that S-alkynyl esters of thioacetic acid are slowly hydrolyzed by acetylcholinesterase and cholinesterase without irreversible inhibition of the enzymes.

[Electroregulated potassium channels of the somatic membrane of mollusk neuron membranes]. / Elektroupravliaemye kalievye kanaly somaticheskoi membrany neironov molliuskov.

The delayed potassium current in mollusc neurons was separated into two components: a noninactivating component and a transient (inactivating) component. A noninactivating potassium current is not affected by changes in temperature, whereas an inactivating component decreases substantially under cooling. Internal Na+ can block the delayed outward potassium current. The blockade of the inactivating potassium current is strongly voltage-dependent. The voltage dependence of the blockade of the noninactivating potassium current is not so clear. These results are consistent with the hypothesis that there are two forms of the delayed potassium current channel. The effect of temperature and internal Na+ on the fast outward current is similar to that on the inactivating component of the delayed potassium current.

[Effect of substituted thiobutinylic esters of phosphorus thio acids and their saturated analogs on cholinesterases of different origins]. / Deistvie nekotorykh zameshchennykh tiobutinilovykh éfirov tiokislot fosfora i ikh nasyshchennykh analogov na kholinésterazy razlichnogo proiskhozhdeniia.

Studies have been made of the effect of organophosphorus inhibitors (OPI) containing butynilic group in the detectable part of the molecule, and of their saturated analogues on cholinesterases from different species of mammals and arthropods. In all cases without a single exception, acetylene compounds exhibited higher anticholinesterase effect than saturated ones. The value of "acetylene effect" varied to a great extent and depended on both the structure of OPI and the source of cholinesterase, these data indicating the existence of differences in the structure of the active site in cholinesterases investigated. The acetylene effect was always higher in ethylmercapto-substituted OPI than in chloride-substituted ones. Among thiophosphates, the highest (7,600) effect was found for cholinesterase of the spider mite in the case of dimethyl esters. Among thiophosphonates, exceptionally high (38,000) effect was noted for cholinesterase from the head of the domestic fly when methylthiophosphonates were compared. In this pair of compounds, the inhibitory constant k2 for the cholinesterase of the fly by acetylene derivative was equal to 1.1 . 10(9).