Products of heme-catalyzed transformation of the arachidonate derivative 12-HPETE open S-type K+ channels in Aplysia. Neuron 1989 Oct;3(4):497-505
Date
10/01/1989Pubmed ID
2642008DOI
10.1016/0896-6273(89)90208-0Scopus ID
2-s2.0-0024745316 60 CitationsAbstract
In Aplysia mechanosensory neurons, the neuropeptide FMRFamide increases the opening of the background S-K+ channel. This action is mediated by activation of arachidonic acid metabolism. Arachidonic acid in Aplysia nervous tissue is transformed through the 12-lipoxygenase pathway to 12-HPETE, which undergoes further metabolism. In intact sensory cells, 12-HPETE simulates the FMRFamide response, raising the question of whether 12-HPETE is the messenger molecule ultimately acting on the S-K+ channel. Here we show that in cell-free (inside-out) patches from sensory cells, 12-HPETE fails to modulate the S-K+ channel, but in the presence of hematin (which catalyzes 12-HPETE metabolism), it triggers sharp increases in the channel opening probability. We also found that SKF-525A, an inhibitor of the cytochrome P450, reduces the response to FMRFamide, arachidonic acid, and 12-HPETE in intact cells. We conclude that a heme-catalyzed transformation of 12-HPETE is necessary and sufficient to promote the opening of the S-K+ channel and a heme-containing enzyme such as cytochrome P450 might play this key role.
Author List
Belardetti F, Campbell WB, Falck JR, Demontis G, Rosolowsky MAuthor
William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAplysia
Arachidonic Acids
Cell-Free System
FMRFamide
Heme
Hemin
Leukotrienes
Neuropeptides
Potassium Channels
Pyridines
