| Summary: | 碩士 === 國立臺灣大學 === 生理學研究所 === 86 === Abstract
Arachidonic acid (AA) and its metabolites have been shown to have impo
rtant physiological or patho-physiological functions in neurons. In the presen
t study, we used BCECF and Fura-2, respectively, to measure intracellular pH (
pHi) or calcium ([Ca2+]i) in rat cerebellar granule cells. We found that an in
tracellular acidification (~0.3 pH unit) can be induced on addition of 10 M
AA. Since the effect of pHi plays an important role on the neuronal function,
we decided to further investigate the cellular mechanism for AA-induced intrac
ellular acidosis. The following possible mechanisms have been ruled out: the i
nvolvement of (i). the pHi-transporters, (ii). intracellular Ca2+ ions, (iii).
AA metabolites, (iv). free radicals, (v). lactate overproduction, (vi). PKC a
ctivation (vii). an increase in proton conductance. The acidification induced
by AA is possibly due to a "flip" mechanism (passive diffusion), which has bee
n suggested by Hamilton and his colleagues in the studies using lipid bilayer
or adipocytes. Our evidence as follows: (i). no effect on the pHi of AA methyl
ester, (ii). other fatty acids have similar effect on the pHi as that seen wi
th AA, (iii). the acidosis-induced by AA can be largely reversed by bovine ser
um albumin (BSA), (iv). a linear relationship between external AA concentratio
ns and the initial rate of AA-induced acidosis. Since the effect of BSA on the
removal of AA was largely abolished when the acid extrusion mechanism was inh
ibited by Na+-free medium, it is suggested that the cytosolic AA was not easil
y to be removed by extracellular BSA. This result also suggests that the "flop
" theory should be modified.
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