Angiotensin II Increases Neuronal Delayed Rectifier K+ Current: Role of 12-Lipoxygenase Metabolites of Arachidonic Acid

Mingyan Zhu, Rama Natarajan, Jerry L. Nadler, Jennifer M. Moore, Craig H. Gelband, Colin Sumners
2000 Journal of Neurophysiology  
II increases neuronal delayed rectifier K ϩ current: role of 12-lipoxygenase metabolites of arachidonic acid. J Neurophysiol 84: 2494 -2501, 2000. Angiotensin II (Ang II) elicits an Ang II type 2 (AT 2 ) receptormediated increase in voltage-dependent delayed rectifier K ϩ current (I KV ) in neurons cultured from newborn rat hypothalamus and brain stem. In previous studies, we have determined that this effect of Ang II is mediated via a Gi protein, activation of phospholipase A 2 (PLA 2 ), and
more » ... A 2 (PLA 2 ), and generation of arachidonic acid (AA). AA is rapidly metabolized within cells via lipoxygenases (LO), cyclooxygenase (COX) or p450 monooxygenase enzymes, and the metabolic products are known regulators of K ϩ currents and channels. Thus in the present study, we have investigated whether the AT 2 receptor-mediated effects of Ang II on neuronal I KV require AA metabolism and if so, which metabolic pathways are involved. The data presented here indicate that the stimulatory actions of Ang II and AA on neuronal I KV are attenuated by selective blockade of 12-LO enzymes. However, the effects of Ang II are not altered by blockade of 5-LO or p450 monooxygenase enzymes. Furthermore, the actions of Ang II are mimicked by a 12-LO metabolite of AA, but 5-LO metabolites such as leukotriene B 4 and C 4 do not alter neuronal I KV . These data indicate that the AT 2 receptor-mediated stimulation of neuronal I KV is partially mediated through 12-LO metabolites of AA.
doi:10.1152/jn.2000.84.5.2494 pmid:11067992 fatcat:sp37pgj6wrcw3afhyfl2nk6gla