The Journal of Neurophysiology Vol. 84 No. 5 November 2000, pp. 2494-2501
Copyright ©2000 by the American Physiological Society
Angiotensin II Increases Neuronal Delayed Rectifier
K+ Current: Role of 12-Lipoxygenase Metabolites of
Arachidonic Acid
Mingyan
Zhu,1
Rama
Natarajan,2
Jerry L.
Nadler,3
Jennifer M.
Moore,1
Craig H.
Gelband,1 and
Colin
Sumners1
1Department of Physiology, College of
Medicine and University of Florida Brain Institute, University of
Florida, Gainesville, Florida 32610; 2Gonda
Diabetes Center, City of Hope Medical Center, Duarte, California 91010;
and 3Division of Endocrinology, University of
Virginia Health Science Center, Charlottesville, Virginia 22908
Zhu, Mingyan,
Rama Natarajan,
Jerry L. Nadler,
Jennifer M. Moore,
Craig H. Gelband, and
Colin Sumners.
Angiotensin II Increases Neuronal Delayed Rectifier
K+ 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 (AT2) receptor-mediated increase in
voltage-dependent delayed rectifier K+ current
(IKV) 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 A2
(PLA2), 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+ currents and
channels. Thus in the present study, we have investigated whether the
AT2 receptor-mediated effects of Ang II on
neuronal IKV 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
IKV 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 B4 and
C4 do not alter neuronal
IKV. These data indicate that the
AT2 receptor-mediated stimulation of neuronal
IKV is partially mediated through
12-LO metabolites of AA.
