The Mechanism of Arachidonic Acid Induced Intracellular Acidification in Rat Cardiomyocytes

• Main Authors: Chan, Chih-Chiang, 詹智強
• Other Authors: Wu, Mei-Lin
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/77243153082907821093

碩士 === 國立臺灣大學 === 生理學研究所 === 87 === Arachidonic acid﹙AA﹚and its metabolites have been shown to have important physiological or patho-physiological functions in the heart. In the present study, we used BCECF to measure intracellular pH﹙pHi﹚in both neonatal and adult rat cardiac myocytes. We found that an intracellular acidification﹙~0.4 & 0.3 pH unit respectively in neonatal and adult myocytes﹚ can be induced on addition of 10 μM AA. Since the effect of pHi plays an important role on cardiac functions, we decided to further investigate the cellular mechanism for AA-induced intracellular acidosis. The following possible mechanisms have been ruled out: the involvement of ﹙i﹚ pHi regulators, ﹙ii﹚ intracellular calcium, ﹙iii﹚ activation of protein kinase C﹙PKC﹚, ﹙iv﹚ AA metabolites, ﹙v﹚ free radicals, ﹙vi﹚ stimulation of NADPH oxidase, ﹙vii﹚ an increase in the proton conductance. The acidification induced by AA is possibly due to a "flip" mechanism ﹙passive diffusion﹚, which have been suggested by Hamilton and his colleagues in the studies using lipid bilayer or adipocytes. Our evidence as follows: ﹙i﹚ no effect of AA methyl ester on the pHi, ﹙ii﹚ TDA﹙tetradecylamine﹚ causes the raise of pHi, ﹙iii﹚ other fatty acids have similar effect on the pHi as that seen with AA, ﹙iv﹚ AA-induced pHi decrease can be largely reversed by bovine serum albumin﹙BSA﹚. Since the effect of BSA on the removal of AA was partially abolished when the acid extrusion mechanism was inhibited by Na+-free medium, it is suggested that the cytosolic AA was not easily to be removed by extracellular BSA. This result also suggests that the "flop" theory should be modified.