Arachidonic acid metabolites inhibit the stimulatory effect of angiotensin II in renal proximal tubules. Export

@article{citeulike:5717808, abstract = {Angiotensin II (Ang II) regulates renal proximal transport in a biphasic way via Ang II type 1 receptor (AT1). Whereas extracellular signal-regulated kinase (ERK) activation mediates the stimulatory effect, cytosolic phospholipase A2 (cPLA2) mediates the inhibitory effect independently of ERK. In this study, we tested the hypothesis that the cPLA2/P450 epoxygenase pathway might work to suppress the Ang II-mediated ERK activation. In the presence of arachidonic acid or 5,6-epoxyeicosatrienoic acid (EET), Ang II failed to stimulate the Na-HCO3 cotransporter activity in renal proximal tubules isolated from wild-type, AT1A-deficient, and cPLA2-alpha-deficient mice. In addition, Ang II failed to induce a significant ERK phosphorylation in the presence of arachidonic acid or 5,6-EET. Arachidonic acid or 5,6-EET also suppressed the stimulatory effect of Ang II on net proximal tubule bicarbonate absorption without changing cell Ca2+ concentrations. These results indicate that the cPLA2-alpha/P450/EET pathway blocks the stimulatory effect of Ang II by suppressing the ERK activation. Thus, the cPLA2-alpha/P450/EET pathway may operate as a unique negative feedback mechanism to attenuate excessive Ang II activity in the renal proximal tubules, where extremely high concentrations of Ang II are found.}, author = {Li, Yuehong and Yamada, Hideomi and Kita, Yoshihiro and Suzuki, Masashi and Endo, Yoko and Horita, Shoko and Yamazaki, Osamu and Shimizu, Takao and Seki, George and Fujita, Toshiro}, citeulike-article-id = {5717808}, citeulike-linkout-0 = {http://dx.doi.org/10.1291/hypres.31.2155}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19139605}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19139605}, doi = {10.1291/hypres.31.2155}, issn = {0916-9636}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, keywords = {aa, aii, pla2, pt}, month = {December}, number = {12}, pages = {2155--2164}, posted-at = {2009-09-03 13:47:07}, priority = {2}, title = {Arachidonic acid metabolites inhibit the stimulatory effect of angiotensin II in renal proximal tubules.}, url = {http://dx.doi.org/10.1291/hypres.31.2155}, volume = {31}, year = {2008} }

TY - JOUR ID - citeulike:5717808 L3 - citeulike-article-id:5717808 N2 - Angiotensin II (Ang II) regulates renal proximal transport in a biphasic way via Ang II type 1 receptor (AT1). Whereas extracellular signal-regulated kinase (ERK) activation mediates the stimulatory effect, cytosolic phospholipase A2 (cPLA2) mediates the inhibitory effect independently of ERK. In this study, we tested the hypothesis that the cPLA2/P450 epoxygenase pathway might work to suppress the Ang II-mediated ERK activation. In the presence of arachidonic acid or 5,6-epoxyeicosatrienoic acid (EET), Ang II failed to stimulate the Na-HCO3 cotransporter activity in renal proximal tubules isolated from wild-type, AT1A-deficient, and cPLA2-alpha-deficient mice. In addition, Ang II failed to induce a significant ERK phosphorylation in the presence of arachidonic acid or 5,6-EET. Arachidonic acid or 5,6-EET also suppressed the stimulatory effect of Ang II on net proximal tubule bicarbonate absorption without changing cell Ca2+ concentrations. These results indicate that the cPLA2-alpha/P450/EET pathway blocks the stimulatory effect of Ang II by suppressing the ERK activation. Thus, the cPLA2-alpha/P450/EET pathway may operate as a unique negative feedback mechanism to attenuate excessive Ang II activity in the renal proximal tubules, where extremely high concentrations of Ang II are found. IS - 12 JF - Hypertension research : official journal of the Japanese Society of Hypertension SN - 0916-9636 EP - 2164 TI - Arachidonic acid metabolites inhibit the stimulatory effect of angiotensin II in renal proximal tubules. VL - 31 SP - 2155 KW - aa KW - aii KW - pla2 KW - pt AU - Li, Yuehong AU - Yamada, Hideomi AU - Kita, Yoshihiro AU - Suzuki, Masashi AU - Endo, Yoko AU - Horita, Shoko AU - Yamazaki, Osamu AU - Shimizu, Takao AU - Seki, George AU - Fujita, Toshiro PY - 2008/12// UR - http://dx.doi.org/10.1291/hypres.31.2155 ER -