Evidence for a membrane site of action for 14,15-EET on expression of aromatase in vascular smooth muscle.
Epoxyeicosatrienoic acids (EETs) are synthesized in the endothelial cells of vascular tissues. They are released from the endothelial cells and produce relaxation of the smooth muscle cells by hyperpolarization. The present findings demonstrate that EETs also regulate aromatase activity in vascular smooth muscle cells. Exposure of cultured rat aortic smooth muscle cells to either 1 microM 14,15-EET or 1 microM 11,12-EET inhibits dibutyryl cAMP-induced aromatase activity by 80-100%. 11,12-Dihydroxyeicosatrienoic acid, the hydration product of 11,12-EET, has no effect on dibutyryl cAMP-induced vascular smooth muscle aromatase activity. In contrast to 14,15-EET, the N-methylsulfanilamide derivative of 14,15-EET (14,15-EET-SA) was neither metabolized nor incorporated into cell lipids, but it retained the ability to inhibit cAMP-induced aromatase activity. Furthermore, the 14,15-EET-SA inhibition of cAMP-induced aromatase activity persisted when the sulfanilamide derivative of 14,15-EET was covalently tethered to silica beads (average diameter, 0.5 microm), which restricted 14,15-EET-SA from entering the cell. These data are consistent with the presence of a receptor for EETs in the plasma membrane and support the hypothesis that the inhibition of aromatase by EETs is initiated by the interaction of EET with the putative plasma membrane receptor.
Snyder
Gary D
GD
Department of Biochemistry, 4-403 BSB, University of Iowa, Iowa City, IA 52242, USA. gary-snyder@uiowa.edu
Krishna
U Murali
UM
Falck
J R
JR
Spector
Arthur A
AA
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001141:Aromatase / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D014665:Vasodilator Agents; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D001141:Aromatase; D015126:8,11,14-Eicosatrienoic Acid