[Inhibition by local anesthetics and barbiturates of the active transport of H+ in the synaptic vesicle membranes of the brain].
The effects of local anesthetics and barbiturates on the ATP-dependent H+ transport in synaptic vesicle membranes from rat brain were studied using a fluorescent probe, acridine orange. Local anesthetics depressed the active H+ transport with the following order of potencies: tetracaine trimecaine lidocaine procaine. Respective IC50 values were 0.07, 0.28, 0.46 and 0.60 mM. The local anesthetics also disrupted the endogenous pH gradient seen in the absence of ATP. Barbiturates inhibited the active H+ transport showing IC50 values in the range of 2-5 mM except for benzobarbital and barbital characterized by IC50 values of 0.5 and 20 mM, respectively. The order of potencies was benzobarbital hexobarbital amobarbital pentobarbital phenobarbital barbital. The endogenous pH gradient was not affected by the barbiturates. The results show that local anesthetics disrupt the H+ transport by acting as permeable weak bases (uncouplers) whereas barbiturates are likely to block and anion channel which maintains electroneutrality of the H+ transport in the membrane of synaptic vesicles.
Shukalova
T F
TF
Mel'nik
V I
VI
Glebov
R N
RN
D000165:Acridine Orange; D000244:Adenosine Diphosphate / Q000378:metabolism; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001693:Biological Transport, Active; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D011522:Protons; D051381:Rats; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D000779:Anesthetics, Local; D001463:Barbiturates; D011522:Protons; D000244:Adenosine Diphosphate; D000165:Acridine Orange
Tormozhenie mestnymi anestetikami i barbituratami aktivnogo transportaH+ v membranakh sinapticheskikh puzyr'kov mozga.