PMID- 9425010
OWN - NLM
STAT- MEDLINE
DCOM- 19980203
LR  - 20191025
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 18
IP  - 2
DP  - 1998 Jan 15
TI  - Angiotensin II type 2 receptor stimulation of neuronal delayed-rectifier 
      potassium current involves phospholipase A2 and arachidonic acid.
PG  - 679-86
AB  - Angiotensin II (Ang II) elicits an Ang II type 2 (AT2) receptor-mediated increase 
      in delayed-rectifier K+ current (IK) in neurons cultured from newborn rat 
      hypothalamus and brainstem. This effect involves a pertussis toxin 
      (PTX)-sensitive Gi protein and is abolished by inhibition of serine and threonine 
      phosphatase 2A (PP-2A). Here, we determined that Ang II stimulates 
      [3H]arachidonic acid (AA) release from cultured neurons via AT2 receptors. This 
      effect of Ang II was blocked by inhibition of phospholipase A2 (PLA2) and by PTX. 
      Because AA and its metabolites are powerful modulators of neuronal K+ currents, 
      we investigated the involvement of PLA2 and AA in the AT2 receptor-mediated 
      stimulation of IK by Ang II. Single-cell reverse transcriptase (RT)-PCR analyses 
      revealed the presence of PLA2 mRNA in neurons that responded to Ang II with an 
      increase in IK. The stimulation of neuronal IK by Ang II was attenuated by 
      selective inhibitors of PLA2 and was mimicked by application of AA to neurons. 
      Inhibition of lipoxygenase (LO) enzymes significantly reduced both Ang II- and 
      AA-stimulated IK, and the 12-LO metabolite of AA 12S-hydroxyeicosatetraenoic acid 
      (12S-HETE) stimulated IK. These data indicate the involvement of a PLA2, AA, and 
      LO metabolite intracellular pathway in the AT2 receptor-mediated stimulation of 
      neuronal IK by Ang II. Furthermore, the demonstration that inhibition of PP-2A 
      abolished the stimulatory effects of Ang II, AA, and 12S-HETE on neuronal IK but 
      did not alter Ang II-stimulated [3H]-AA release suggests that PP-2A is a distal 
      event in this pathway.
FAU - Zhu, M
AU  - Zhu M
AD  - Department of Physiology, University of Florida, College of Medicine, 
      Gainesville, Florida 32610, USA.
FAU - Gelband, C H
AU  - Gelband CH
FAU - Moore, J M
AU  - Moore JM
FAU - Posner, P
AU  - Posner P
FAU - Sumners, C
AU  - Sumners C
LA  - eng
GR  - HL49130/HL/NHLBI NIH HHS/United States
GR  - HL52189/HL/NHLBI NIH HHS/United States
GR  - NS19441/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Delayed Rectifier Potassium Channels)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Receptors, Angiotensin)
RN  - 11128-99-7 (Angiotensin II)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Animals
MH  - Arachidonic Acid/*metabolism
MH  - Cells, Cultured
MH  - Delayed Rectifier Potassium Channels
MH  - Neurons/*metabolism
MH  - Phospholipases A/*metabolism
MH  - Phospholipases A2
MH  - Potassium Channels/*metabolism
MH  - *Potassium Channels, Voltage-Gated
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 2
MH  - Receptors, Angiotensin/*metabolism
PMC - PMC6792530
EDAT- 1998/02/07 00:00
MHDA- 1998/02/07 00:01
PMCR- 1998/07/15
CRDT- 1998/02/07 00:00
PHST- 1998/02/07 00:00 [pubmed]
PHST- 1998/02/07 00:01 [medline]
PHST- 1998/02/07 00:00 [entrez]
PHST- 1998/07/15 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.18-02-00679.1998 [doi]
PST - ppublish
SO  - J Neurosci. 1998 Jan 15;18(2):679-86. doi: 10.1523/JNEUROSCI.18-02-00679.1998.