Arachidonic acid potentiates the feedback response of large, ca2+
-activated k channels to angiotensin ii in human glomerular mesangial
cells.
Stockand, James D., Meredith Silverman, David Hall, Thomas Derr, Brian
Kubacak, and Steven C. Sansom.
Departments of Medicine and Integrative Biology, Pharmacology and
Physiology, University of Texas Medical School at Houston and
Department of Physiology, and Biophysics, University of Nebraska
Medical Center
APStracts 5:0008F, 1998.
The influence of arachidonic acid (AA) on the feedback regulation of
mesangial contraction by large Ca2+-activated K+ channels (BKCa) was
determined through single channel analysis using the patch clamp
method. The mesangial BKCa is a low gain negative feedback inhibitor
of contraction that is activated in response to agonist-induced Ca2+
transients and membrane depolarization. Arachidonic acid activated
BKCa in cell attached patches in a dose-dependent manner with a
maximal effect at 400 nM and a half maximal response at 49 nM. In
inside out patches, AA directly activated BKCa with a maximal effect
at 400 nM. BKCa was activated significantly in response to addition
of 100 nM angiotensin II (ANGII) in the presence but not the absence
of AA. Since it was shown previously that fatty acids stimulated both
soluble and membrane-bound guanylyl cyclase, we determined if AA
activated BKCa by interfering with guanosine 3',5'-cyclic
monophosphate (cGMP)-mediated signal transduction pathways. It was
previously shown that 10 [mu]M cGMP, via cGMP-dependent protein
kinase, activated BKCa in a biphasic manner with an early increase in
Po and a subsequent inactivation mediated by phosphoprotein
phosphatase 2A (PP2A). We found that 10 [mu]M dibutyryl cGMP enhanced
BKCa activity in an additive manner with saturating concentrations
(400 nM) of AA. Moreover, the inactivation phase mediated by PP2A was
not abolished. Thus, AA does not affect the
phosphorylation/dephosphorylation regulatory cycle for BKCa. It is
concluded that AA potentiates the ANGII feedback response of BKCa by
a mechanism that is independent of the phosphorylation cycle.
Received 2 May 1997; accepted in final form 9 January 1998.
APS Manuscript Number F150-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 28 January 1998